SMART MODE:

NORMAL GENOMIC

• Bullerwell CE, Burger G, Lang BF
• A novel motif for identifying rps3 homologs in fungal mitochondrial genomes.
• Trends Biochem Sci. 2000; 25: 363-5

• Schenker T, Trueb B
• BSPRY, a novel protein of the Ro-Ret family.
• Biochim Biophys Acta. 2000; 1493: 255-8
• Display abstract

• Utilizing the yeast two-hybrid system we have identified a novel protein of the Ro-Ret family that was termed BSPRY. This protein is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. BSPRY from human beings shares 80% sequence identity with the homologous protein from mice. The gene for BSPRY resides on human chromosome 9 and is specifically expressed in testis. It comprises six exons and five introns and possesses a GC rich promoter forming a typical CpG island. The function of BSPRY is not known, but several related proteins of the RBCC family have been implicated in cell transformation.

• Plomaritoglou A, Choli-Papadopoulou T, Guialis A
• Molecular characterization of a murine, major A/B type hnRNP protein: mBx.
• Biochim Biophys Acta. 2000; 1490: 54-62
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• We have previously identified a discrete hnRNP polypeptide of the A/B type, named mBx, as an abundant protein species in murine cells. The molecular characterization of this protein is now accomplished. From all evidence provided, mBx polypeptide represents a new gene product, distinct from the known members of the A/B family A1 and A2/B1. It is, instead, mostly related to a still hypothetical human protein of A/B type, as well as to the Xenopus hnRNPA3 protein species.

• Apweiler R
• Protein sequence databases.
• Adv Protein Chem. 2000; 54: 31-71

• Bateman A, Birney E
• Searching databases to find protein domain organization.
• Adv Protein Chem. 2000; 54: 137-57

• Das S, Smith TF
• Identifying nature's protein Lego set.
• Adv Protein Chem. 2000; 54: 159-83

• Phakdeekitcharoen B, Watnick TJ, Ahn C, Whang DY, Burkhart B, Germino GG
• Thirteen novel mutations of the replicated region of PKD1 in an Asian population.
• Kidney Int. 2000; 58: 1400-12
• Display abstract

• BACKGROUND: Mutations of PKD1 are thought to account for approximately 85% of all mutations in autosomal dominant polycystic kidney disease (ADPKD). The search for PKD1 mutations has been hindered by both its large size and complicated genomic structure. To date, few mutations that affect the replicated segment of PKD1 have been described, and virtually all have been reported in Caucasian patients. METHODS: In the present study, we have used a long-range polymerase chain reaction (PCR)-based strategy previously developed by our laboratory to analyze exons in the replicated region of PKD1 in a population of 41 unrelated Thai and 6 unrelated Korean families with ADPKD. We have amplified approximately 3.5 and approximately 5 kb PKD1 gene-specific fragments (5'MR and 5'LR) containing exons 13 to 15 and 15 to 21 and performed single-stand conformation analysis (SSCA) on nested PCR products. RESULTS: Nine novel pathogenic mutations were detected, including six nonsense and three frameshift mutations. One of the deletions was shown to be a de novo mutation. Four potentially pathogenic variants, including one 3 bp insertion and three missense mutations, were also discovered. Two of the nonconservative amino acid substitutions were predicted to disrupt the three-dimensional structure of the PKD repeats. In addition, six polymorphisms, including two missense and four silent nucleotide substitutions, were identified. Approximately 25% of both the pathogenic and normal variants were found to be present in at least one of the homologous loci. CONCLUSION: To our knowledge, this is the first report of mutation analysis of the replicated region of PKD1 in a non-Caucasian population. The methods used in this study are widely applicable and can be used to characterize PKD1 in a number of ethnic groups using DNA samples prepared using standard techniques. Our data suggest that gene conversion may play a significant role in producing variability of the PKD1 sequence in this population. The identification of additional mutations will help guide the study of polycystin-1 and better help us to understand the pathophysiology of this common disease.

• Sims JE
• CD121a.
• J Biol Regul Homeost Agents. 2000; 14: 133-5

• Heger A, Holm L
• Rapid automatic detection and alignment of repeats in protein sequences.
• Proteins. 2000; 41: 224-37
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• Many large proteins have evolved by internal duplication and many internal sequence repeats correspond to functional and structural units. We have developed an automatic algorithm, RADAR, for segmenting a query sequence into repeats. The segmentation procedure has three steps: (i) repeat length is determined by the spacing between suboptimal self-alignment traces; (ii) repeat borders are optimized to yield a maximal integer number of repeats, and (iii) distant repeats are validated by iterative profile alignment. The method identifies short composition biased as well as gapped approximate repeats and complex repeat architectures involving many different types of repeats in the query sequence. No manual intervention and no prior assumptions on the number and length of repeats are required. Comparison to the Pfam-A database indicates good coverage, accurate alignments, and reasonable repeat borders. Screening the Swissprot database revealed 3,000 repeats not annotated in existing domain databases. A number of these repeats had been described in the literature but most were novel. This illustrates how in times when curated databases grapple with ever increasing backlogs, automatic (re)analysis of sequences provides an efficient way to capture this important information.

• Heger A, Holm L
• Towards a covering set of protein family profiles.
• Prog Biophys Mol Biol. 2000; 73: 321-37
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• Evolutionary classification leads to an economical description of the protein sequence universe because attributes of function and structure are inherited in protein families. Efficient strategies of functional and structural genomics therefore target one representative from each family. Enumerating all families and establishing family membership consistently based on sequence similarities are nontrivial computational problems. Emerging concepts and caveats of global sequence clustering are reviewed. Explicit multiple alignments coupled with neighbourhood analysis lead to domain segmentation, and hierarchical unification helps to resolve conflicts and validate clusters. Eventually, every part of every sequence will be assigned to a domain family which is uniquely associated with a fold and a molecular function.

• Dinulescu DM, Cone RD
• Agouti and agouti-related protein: analogies and contrasts.
• J Biol Chem. 2000; 275: 6695-8

• Pritchard L et al.
• A human PKD1 transgene generates functional polycystin-1 in mice and is associated with a cystic phenotype.
• Hum Mol Genet. 2000; 9: 2617-27
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• Three founder transgenic mice were generated with a 108 kb human genomic fragment containing the entire autosomal dominant polycystic kidney disease (ADPKD) gene, PKD1, plus the tuberous sclerosis gene, TSC2. Two lines were established (TPK1 and TPK3) each with approximately 30 copies of the transgene. Both lines produced full-length PKD1 mRNA and polycystin-1 protein that was developmentally regulated, similar to the endogenous pattern, with expression during renal embryogenesis and neonatal life, markedly reduced at the conclusion of renal development. Tuberin expression was limited to the brain. Transgenic animals from both lines (and the TPK2 founder animal) often displayed a renal cystic phenotype, typically consisting of multiple microcysts, mainly of glomerular origin. Hepatic cysts and bile duct proliferation, characteristic of ADPKD, were also seen. All animals with two copies of the transgenic chromosome developed cysts and, in total, 48 of the 100 transgenic animals displayed a cystic phenotype. To test the functionality of the transgene, animals were bred with the Pkd1(del34) knockout mouse. Both transgenic lines rescued the embryonically lethal Pkd1(del34/del34) phenotype, demonstrating that human polycystin-1 can complement for loss of the endogenous protein. The rescued animals were viable into adulthood, although more than half developed hepatic cystic disease in later life, similar to the phenotype of older Pkd1(del34/+) animals. The TPK mice have defined a minimal area that appropriately expresses human PKD1. Furthermore, this model indicates that over-expression of normal PKD1 can elicit a disease phenotype, suggesting that the level of polycystin-1 expression may be relevant in the human disease.

• Hanaoka K et al.
• Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents.
• Nature. 2000; 408: 990-4
• Display abstract

• The human kidney is composed of roughly 1.2-million renal tubules that must maintain their tubular structure to function properly. In autosomal dominant polycystic kidney disease (ADPKD) cysts develop from renal tubules and enlarge independently, in a process that ultimately causes renal failure in 50% of affected individuals. Mutations in either PKD1 or PKD2 are associated with ADPKD but the function of these genes is unknown. PKD1 is thought to encode a membrane protein, polycystin-1, involved in cell-cell or cell-matrix interactions, whereas the PKD2 gene product, polycystin-2, is thought to be a channel protein. Here we show that polycystin-1 and -2 interact to produce new calcium-permeable non-selective cation currents. Neither polycystin-1 nor -2 alone is capable of producing currents. Moreover, disease-associated mutant forms of either polycystin protein that are incapable of heterodimerization do not result in new channel activity. We also show that polycystin-2 is localized in the cell in the absence of polycystin-1, but is translocated to the plasma membrane in its presence. Thus, polycystin-1 and -2 co-assemble at the plasma membrane to produce a new channel and to regulate renal tubular morphology and function.

• Panchin Y, Kelmanson I, Matz M, Lukyanov K, Usman N, Lukyanov S
• A ubiquitous family of putative gap junction molecules.
• Curr Biol. 2000; 10: 4734-4734

• Knight RD, Landweber LF
• The early evolution of the genetic code.
• Cell. 2000; 101: 569-72

• Shapiro L, Harris T
• Finding function through structural genomics.
• Curr Opin Biotechnol. 2000; 11: 31-5
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• The recent availability of whole-genome sequences and large numbers of protein-coding regions from high-throughput cDNA analysis has fundamentally changed experimental biology. These efforts have provided huge databases of protein sequences, many of which are of unknown function. Deciphering the functions of these myriad proteins presents a major intellectual challenge.

• Higgins DG, Taylor WR
• Multiple sequence alignment.
• Methods Mol Biol. 2000; 143: 1-18

• Hoersch S, Leroy C, Brown NP, Andrade MA, Sander C
• The GeneQuiz web server: protein functional analysis through the Web.
• Trends Biochem Sci. 2000; 25: 33-5

• Sansom MS, Davison L
• Modeling transmembrane helix bundles by restrained MD simulations.
• Methods Mol Biol. 2000; 143: 325-47

• Telliez JB, Bean KM, Lin LL
• LRDD, a novel leucine rich repeat and death domain containing protein.
• Biochim Biophys Acta. 2000; 1478: 280-8
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• Death domains (DD) and leucine rich repeats (LRR) are two different types of protein interaction motifs. Death domains are found predominantly in proteins involved in signaling and are involved in homo- and heteromultimerization. Leucine rich repeats are found in proteins with diverse cellular functions, like cell adhesion and cellular signaling, and mediate reversible protein-protein interactions. In this paper we report the cloning of a new human gene called LRDD (leucine repeat death domain containing protein). LRDD encodes a protein of 83 kDa with six LRRs at the N-terminus and a DD at the C-terminus. LRDD appears to be processed into two fragments of about 33 and 55 kDa, containing LRRs and DD respectively. Interestingly, LRDD is shown to interact with two other death domain containing proteins, FADD and MADD, presumably through death domain interactions. LRDD may represent a new type of adapter protein that could be involved in signaling or other cellular functions.

• Ong AC
• Cyst formation in ADPKD: new insights from natural and targeted mutants.
• Nephrol Dial Transplant. 1999; 14: 544-6

• Maekawa K
• Informational symmetry breaking between proteins and nucleic acids.
• Biosystems. 1999; 51: 21-9
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• Anti-symmetry of the information-processing mechanisms between proteins and nucleic acids is generalized to informational symmetry breaking between a genetic polymer and an anti-genetic polymer so as not to depend on particular chemical species. In a genetic polymer, e.g. nucleic acids, any sequence can form a closed double-stranded structure with a specific partner sequence. On the other hand, in an anti-genetic polymer, e.g. proteins, a chain could fold to an open multi-stranded structure and reinterpretation of the genetic information through slides or shifts between stacked strands could be induced by external perturbations. The possibility of the informational symmetry breaking by hierarchical organization of a single chemical species, i.e. polypeptides as a genetic polymer and nucleic acids as an anti-genetic polymer, is examined. The informational functions of genetic polymers and anti-genetic polymers in a complex mixture of macromolecules are characterized.

• Cho SW, Cho EH, Hwang SH, Choi SY
• Reactive cysteine residue of bovine brain glutamate dehydrogenase isoproteins.
• Mol Cells. 1999; 9: 91-8
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• Protein chemical studies of glutamate dehydrogenase isoproteins (GDH I and GDH II) from bovine brain reveal that one cystein residue is accessible for reaction with thiol-modifying reagent. Reaction of the two types of GDH isoproteins with p-chloromercuribenzoic acid resulted in a time-dependent loss of enzyme activity. The inactivation followed pseudo first-order kinetics with the second-order rate constant of 83 M(-1) s(-1) and 75 M(-1) s(-1) for GDH I and GDH II, respectively. The inactivation was partially prevented by preincubation of the glutamate dehydrogenase isoproteins with NADH. A combination of 10 mM 2-oxoglutarate with 2 mM NADH gave complete protection against the inactivation. There were no significant differences between the two glutamate dehydrogenase isoproteins in their sensitivities to inactivation by p-chloromercuribenzoic indicating that the microenvironmental structures of the GDH isoproteins are very similar to each other. Allosteric effectors such as ADP and GTP had no effects on the inactivation of glutamate dehydrogenase isoproteins by thiol-modifying reagents. By a combination of peptide mapping analysis and labeling with [14C] p-chloromercuribenzoic acid, a reactive cystein residue was identified as Cys323 in the overall sequence. The cysteine residue was clearly identical to sequences of other GDH species known.

• Klein C et al.
• Association of a missense change in the D2 dopamine receptor with myoclonus dystonia.
• Proc Natl Acad Sci U S A. 1999; 96: 5173-6
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• Hereditary autosomal dominant myoclonus dystonia (MD) is a movement disorder characterized by involuntary lightning jerks and dystonic movements and postures alleviated by alcohol. Although various large families with MD have been described, no positive linkage has been found to a chromosomal location. We report a family with eight members with MD. Linkage analysis identified a 23-centimorgan region on chromosome 11q23 that cosegregates with the disease state (maximum multipoint logarithm of odds score = 2.96 at D11S897). This region contains an excellent candidate gene for involvement in the etiology of MD, the D2 dopamine receptor (DRD2) gene. Neurotransmission mediated by DRD2 is known to have a key role in the control of movement and also has been implicated in reward and reinforcement mechanisms and psychiatric disorders. Sequencing of the coding region of DRD2 indicated that all affected and obligate carriers were heterozygous for a Val154Ile change in exon 3 of the protein, which is highly conserved across species. This change was found neither in other unaffected members of the pedigree nor in 250 control chromosomes. Our finding provides evidence for the involvement of DRD2 in a disorder of the central nervous system and should lead to further insight into the function of the dopaminergic system in dystonia and other movement and mood disorders.

• Conlon JM
• Molecular diversity, localization, and biological actions of elasmobranch tachykinins.
• J Exp Zool. 1999; 284: 535-40

• Mann K, Siedler F
• The amino acid sequence of ovocleidin 17, a major protein of the avian eggshell calcified layer.
• Biochem Mol Biol Int. 1999; 47: 997-1007
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• The amino acid sequence of ovocleidin 17, a major protein of the chicken eggshell calcified layer, contains 142 amino acids including 2 phosphorylated serines. Data base searches show that ovocleidin belongs to a heterogeneous group of proteins consisting of a single C-type lectin domain (CTL). The most similar sequences with an average of 30% identical amino acids were those of pancreatic stone protein (lithostathine) and lectins and anticoagulant proteins from snake venom.

• Komori Y, Nikai T, Tohkai T, Sugihara H
• Primary structure and biological activity of snake venom lectin (APL) from Agkistrodon p. piscivorus (Eastern cottonmouth).
• Toxicon. 1999; 37: 1053-64
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• A lectin (APL) was purified from the venom of Agkistrodon piscivorus piscivorus (Eastern cottonmouth moccasin). APL is a disulfide-linked, homodimeric protein consisting of identical monomers of molecular weight 16,200. Native rabbit and human erythrocytes were agglutinated by APL and the activity was found to be calcium-dependent. Galactose, lactose, rhamnose and EGTA strongly inhibited the hemagglutination activity of APL. The complete amino acid sequence determined by Edman sequencing of the S-pyridylethylated derivative and its peptides derived from enzymatic digestion indicate the structure of APL to be highly homologous with lectins and the platelet glycoprotein Ib (GPIb)-binding proteins isolated from other snake venoms. These results suggest that APL belongs to the C-type beta-galactoside binding lectin family which possess structural similarities with the C-terminal carbohydrate-recognition domain (CRD) of animal membrane lectins.

• Ong AC et al.
• Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2/PKD1 cystic tissue.
• Kidney Int. 1999; 56: 1324-33
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• BACKGROUND: The mutational mechanism responsible for cyst formation in polycystic kidney disease 1 gene (PKD1) remains controversial, with data indicating a two-hit mechanism, but also evidence of polycystin-1 expression in cystic tissue. METHODS: To investigate this apparent paradox, we analyzed polycystin-1 expression in cystic renal or liver tissue from 10 patients with truncating PKD1 mutations (including one early-onset case) and 2 patients with severe disease associated with contiguous deletions of TSC2 and PKD1, using monoclonal antibodies (mAbs) to both extreme N-(7e12) and C-terminal (PKS-A) regions of the protein. Truncation of the C-terminal epitope from the putative mutant proteins in each case allowed exclusive assessment of the nontruncated protein with PKS-A. RESULTS: In adult PKD1 tissue, the majority of cysts (approximately 80%) showed polycystin-1 expression, although staining was absent in a variable but significant minority (approximately 20%), in spite of the normal expression of marker proteins. Unlike adult PKD1, however, negative cysts were rarely found in infantile PKD1 or TSC2/PKD1 deletion cases. CONCLUSIONS: If a two-hit mutational mechanism is operational, these results suggest that the majority of somatic mutations in adult PKD1 are likely to be missense changes. The low level of polycystin-1-negative cysts in the three "early-onset" cases, however, suggests that a somatic PKD1 mutation may not always be required for cyst formation.

• Yamazoe Y, Nagata K, Yoshinari K, Fujita K, Shiraga T, Iwasaki K
• Sulfotransferase catalyzing sulfation of heterocyclic amines.
• Cancer Lett. 1999; 143: 103-7
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• Cytosolic sulfation of arylamines to form sulfamates is found to be mediated by sulfotransferases of three gene families (SULT1 to 3). Among them, a SULT3 form (ST3A1) showed a high selectivity for N-sulfation of N-substituted aryl and alicyclic compounds. SULT1 (phenol) and SULT2 (hydroxysteroid) sulfotransferases showed N-sulfating activities of carcinogenic heterocyclic amines. For N-hydroxyarylamine O-sulfation, SULT1 forms showed high activity. In rats, ST1C1 mediated the metabolic activation of N-hydroxyarylamines. However, the related form (ST1C2) in humans showed the negligible activity. Instead, ST1A3 showed high metabolic activating abilities among human sulfotransferases.

• Stix G
• Parsing cells.
• Sci Am. 1999; 281: 35-6

• Hahn Y, Lee J, Seong C, Yoon J, Chung JH
• Structural analysis of phylogenetically conserved J domain protein gene.
• Biochim Biophys Acta. 1999; 1447: 325-33
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• Novel cDNAs encoding evolutionarily conserved J Domain Proteins (JDPs) were investigated from Drosophila and mouse. Each of the full coding sequences potentially encodes a conserved J domain, but lacks additional characteristic structures present in DnaJ family proteins. The expression was restricted to head in Drosophila. However, ubiquitous expression was observed in mice with the highest level in kidney.

• Tsiokas L, Arnould T, Zhu C, Kim E, Walz G, Sukhatme VP
• Specific association of the gene product of PKD2 with the TRPC1 channel.
• Proc Natl Acad Sci U S A. 1999; 96: 3934-9
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• The function(s) of the genes (PKD1 and PKD2) responsible for the majority of cases of autosomal dominant polycystic kidney disease is unknown. While PKD1 encodes a large integral membrane protein containing several structural motifs found in known proteins involved in cell-cell or cell-matrix interactions, PKD2 has homology to PKD1 and the major subunit of the voltage-activated Ca2+ channels. We now describe sequence homology between PKD2 and various members of the mammalian transient receptor potential channel (TRPC) proteins, thought to be activated by G protein-coupled receptor activation and/or depletion of internal Ca2+ stores. We show that PKD2 can directly associate with TRPC1 but not TRPC3 in transfected cells and in vitro. This association is mediated by two distinct domains in PKD2. One domain involves a minimal region of 73 amino acids in the C-terminal cytoplasmic tail of PKD2 shown previously to constitute an interacting domain with PKD1. However, distinct residues within this region mediate specific interactions with TRPC1 or PKD1. The C-terminal domain is sufficient but not necessary for the PKD2-TRPC1 association. A more N-terminal domain located within transmembrane segments S2 and S5, including a putative pore helical region between S5 and S6, is also responsible for the association. Given the ability of the TRPC to form functional homo- and heteromultimeric complexes, these data provide evidence that PKD2 may be functionally related to TRPC proteins and suggest a possible role of PKD2 in modulating Ca2+ entry in response to G protein-coupled receptor activation and/or store depletion.

• Blaszak RT, Potaman V, Sinden RR, Bissler JJ
• DNA structural transitions within the PKD1 gene.
• Nucleic Acids Res. 1999; 27: 2610-7
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• Autosomal dominant polycystic kidney disease (ADPKD) affects over 500 000 Americans. Eighty-five percent of these patients have mutations in the PKD1 gene. The focal nature of cyst formation has recently been attributed to innate instability in the PKD1 gene. Intron 21 of this gene contains the largest polypurine. polypyrimidine tract (2.5 kb) identified to date in the human genome. Polypurine.polypyrimidine mirror repeats form intramolecular triplexes, which may predispose the gene to mutagenesis. A recombinant plasmid containing the entire PKD1 intron 21 was analyzed by two-dimensional gel electrophoresis and it exhibited sharp structural transitions under conditions of negative supercoiling and acidic pH. The superhelical density at which the transition occurred was linearly related to pH, consistent with formation of protonated DNA structures. P1 nuclease mapping studies of a plasmid containing the entire intron 21 identified four single-stranded regions where structural transitions occurred at low superhelical densities. Two-dimensional gel electrophoresis and chemical modification studies of the plasmid containing a 46 bp mirror repeat from one of the four regions demonstrated the formation of an H-y3 triplex structure. In summary, these experiments demonstrate that a 2500 bp polypurine.polypyrimidine tract within the PKD1 gene is capable of forming multiple non-B-DNA structures.

• Gouet P, Courcelle E, Stuart DI, Metoz F
• ESPript: analysis of multiple sequence alignments in PostScript.
• Bioinformatics. 1999; 15: 305-8
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• MOTIVATION: The program ESPript (Easy Sequencing in PostScript) allows the rapid visualization, via PostScript output, of sequences aligned with popular programs such as CLUSTAL-W or GCG PILEUP. It can read secondary structure files (such as that created by the program DSSP) to produce a synthesis of both sequence and structural information. RESULTS: ESPript can be run via a command file or a friendly html-based user interface. The program calculates an homology score by columns of residues and can sort this calculation by groups of sequences. It offers a palette of markers to highlight important regions in the alignment. ESPript can also paste information on residue conservation into coordinate files, for subsequent visualization with a graphics program. AVAILABILITY: ESPript can be accessed on its Web site at http://www.ipbs.fr/ESPript. Sources and helpfiles can be downloaded via anonymous ftp from ftp.ipbs.fr. A tar file is held in the directory pub/ESPript.

• Bentz J, Baucom A, Hansen M, Gregoret L
• DINAMO: interactive protein alignment and model building.
• Bioinformatics. 1999; 15: 309-16
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• MOTIVATION: To facilitate the process of structure prediction by both comparative modeling and fold recognition, we describe DINAMO, an interactive protein alignment building and model evaluation tool that dynamically couples a multiple sequence alignment editor to a molecular graphics display. DINAMO allows the user to optimize the alignment and model to satisfy the known heuristics of protein structure by means of a set of analysis tools. The analysis tools return information to both the alignment editor and graphics model in the form of visual cues (color, shape), allowing for rapid evaluation. Several analysis tools may be employed, including residue conservation, residue properties (charge, hydrophobicity, volume), residue environmental preference, and secondary structure propensity. RESULTS: We demonstrate DINAMO by building a model for submission in the 3rd annual Critical Assessment of Techniques for Protein Structure Prediction (CASP3) contest. AVAILABILITY: DINAMO is freely available as a local application or Web-based Java applet at http://tito.ucsc.edu/dinamo

• Wilson PD, Geng L, Li X, Burrow CR
• The PKD1 gene product, "polycystin-1," is a tyrosine-phosphorylated protein that colocalizes with alpha2beta1-integrin in focal clusters in adherent renal epithelia.
• Lab Invest. 1999; 79: 1311-23
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• Mutations in the PKD1 gene are responsible for autosomal dominant polycystic kidney disease (ADPKD). Although PKD1 has been cloned and shown to be expressed at high levels in the fetal ureteric bud and ADPKD cystic epithelia in the human kidney, the function of its encoded protein, "polycystin-1" is unknown. In this study we used primary and immortalized human renal epithelial cell lines derived from normal fetal, adult, and ADPKD kidneys, that endogenously express PKD1, to study the biologic function of the polycystin-1 protein. ADPKD renal epithelial cells expressed high levels of polycystin-1 protein and showed increased adhesion to type I collagen by comparison with normal adult human renal epithelia that expressed little polycystin. Adherent ADPKD cells also expressed high levels of alpha2beta1-integrin and their attachment was inhibited by a functional monoclonal antibody to alpha2-integrin. Double labeling and confocal microscopy as well as coimmunoprecipitation analysis showed overlapping colocalization of polycystin-1 with alpha2beta1-integrin as well as with the focal adhesion proteins vinculin and paxillin in multiprotein clusters localized to focal areas of cell membrane contact with type I collagen matrix after short periods of attachment. Immunoprecipitation and Western immunoblot studies also showed that polycystin-1 was posttranslationally modified by tyrosine phosphorylation. These studies suggest that the PKD1-encoded protein is part of a large multiprotein complex in epithelial cells that functions in the regulation of extracellular matrix interactions with the plasma membrane and cell cytoskeleton.

• Sugiyama H, Murata K, Iuchi I, Nomura K, Yamagami K
• Formation of mature egg envelope subunit proteins from their precursors (choriogenins) in the fish, Oryzias latipes: loss of partial C-terminal sequences of the choriogenins.
• J Biochem (Tokyo). 1999; 125: 469-75
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• The inner layer of egg envelope of the medaka, Oryzias latipes, comprises two major groups of glycoprotein subunits, ZI-1,2 and ZI-3. Their precursor proteins, choriogenin H (Chg H) and choriogenin L (Chg L), respectively, are synthesized in spawning female liver. In the present study, the primary structures of the precursors and the corresponding mature subunits were compared by peptide mapping and amino acid sequencing to find what difference in their molecular structures is relevant to the assembly of the soluble precursors into the insoluble inner layer. The primary structures of the solubilized subunits were mostly identical to those of the respective precursors, but they lacked C-terminal partial sequences that their precursors possessed, namely, ZI-1,2 subunit was shorter than Chg H by 34 amino acid residues and ZI-3 was shorter than Chg L by 27 residues. In addition, a consensus amino acid sequence, Arg-Lys-X-Arg, was found at the putative cleavage sites in the C-terminal region of the precursors. It is conjectured that the truncation of the precursor proteins is prerequisite for formation of mature chorion subunit proteins and their assembly into chorion.

• Mott R, Tribe R
• Approximate statistics of gapped alignments.
• J Comput Biol. 1999; 6: 91-112
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• A heuristic approximation to the score distribution of gapped alignments in the logarithmic domain is presented. The method applies to comparisons between random, unrelated protein sequences, using standard score matrices and arbitrary gap penalties. It is shown that gapped alignment behavior is essentially governed by a single parameter, alpha, depending on the penalty scheme and sequence composition. This treatment also predicts the position of the transition point between logarithmic and linear behavior. The approximation is tested by simulation and shown to be accurate over a range of commonly used substitution matrices and gap-penalties.

• Paterson AD, Pei Y
• PKD3-to be or not to be?
• Nephrol Dial Transplant. 1999; 14: 2965-6

• Lessel U, Schomburg D
• Importance of anchor group positioning in protein loop prediction.
• Proteins. 1999; 37: 56-64
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• The aim of loop prediction in protein homology modeling is to connect the main chain ends of two successive regions, conserved in template and target structures by protein fragments that are as similar to the target as possible. For the development of a new loop prediction method, examples of insertions and deletions were searched automatically in data sets of structurally aligned protein pairs. Three different criteria were applied for the determination of the positions where the main chain conformations of the proteins begin to differ, i.e., the anchoring groups of the insertions and deletions, giving three test data sets. The target structures in these data sets were predicted by inserting fragments from different fragment data banks between the anchoring groups of the templates. The proposals of matching fragments were sorted with decreasing correspondence in the geometry of the anchoring groups. For assessment of the prediction quality, the template loops were substituted by the proposed ones, and their root mean square deviations to the target structures were determined. In addition, the best 20 fragments in the whole loop data bank used-those with the lowest deviations from the target structures after insertion into the templates-were determined and compared with the proposals. The analysis of the results shows limitations of knowledge-based loop prediction. It is demonstrated that the selection of the anchoring groups is the most important step in the whole procedure. Proteins 1999;37:56-64.

• Cai Y et al.
• Identification and characterization of polycystin-2, the PKD2 gene product.
• J Biol Chem. 1999; 274: 28557-65
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• PKD2, the second gene for the autosomal dominant polycystic kidney disease (ADPKD), encodes a protein, polycystin-2, with predicted structural similarity to cation channel subunits. However, the function of polycystin-2 remains unknown. We used polyclonal antisera specific for the intracellular NH(2) and COOH termini to identify polycystin-2 as an approximately 110-kDa integral membrane glycoprotein. Polycystin-2 from both native tissues and cells in culture is sensitive to Endo H suggesting the continued presence of high-mannose oligosaccharides typical of pre-middle Golgi proteins. Immunofluorescent cell staining of polycystin-2 shows a pattern consistent with localization in the endoplasmic reticulum. This finding is confirmed by co-localization with protein-disulfide isomerase as determined by double indirect immunofluorescence and co-distribution with calnexin in subcellular fractionation studies. Polycystin-2 translation products truncated at or after Gly(821) retain their exclusive endoplasmic reticulum localization while products truncated at or before Glu(787) additionally traffic to the plasma membrane. Truncation mutants that traffic to the plasma membrane acquire Endo H resistance and can be biotinylated on the cell surface in intact cells. The 34-amino acid region Glu(787)-Ser(820), containing two putative phosphorylation sites, is responsible for the exclusive endoplasmic reticulum localization of polycystin-2 and is the site of specific interaction with an as yet unidentified protein binding partner for polycystin-2. The localization of full-length polycystin-2 to intracellular membranes raises the possibility that the PKD2 gene product is a subunit of intracellular channel complexes.

• Martinez-Anso E, Lostao MP, Martinez JA
• Immunohistochemical localization of leptin in rat kidney.
• Kidney Int. 1999; 55: 1129-30

• Kisselev LL, Frolova LY
• Termination of translation in eukaryotes: new results and new hypotheses.
• Biochemistry (Mosc). 1999; 64: 8-16
• Display abstract

• Important new results obtained in studies of prokaryotic and eukaryotic translation termination during 1994-1998 are reviewed. Properties of the newly discovered factors RF3, eRF1, and eRF3 are described. Similarity and difference between prokaryotic and eukaryotic systems of translation termination and recent models of molecular mechanisms of protein synthesis at the termination stage are discussed. Hypotheses concerning the biological role of eRF3 are formulated and discussed.

• Korotkov EV, Korotkova MA, Rudenko VM, Skriabin KG
• [Regions with latent periodicity in protein amino acid sequences]
• Mol Biol (Mosk). 1999; 33: 688-95

• Roitberg MA, Semionenkov MN, Tabolina OI
• [Pareto-optimal alignment of biological sequences]
• Biofizika. 1999; 44: 581-94
• Display abstract

• The problem of alignment of two symbol sequences is considered. The validity of the available algorithms for constructing optimal alignment depends on the weighting coefficients which are frequently difficult to choose. A new approach to the problem is proposed, which is based on the use of vector weighting functions (instead of tradionally used scalar ones) and Pareto-optimal alignment (an alignment that is optimal at any choice of weighting coefficient will always be Pareto-optimal). An efficient algorithm for constructing all Pareto-optimal alignments of two sequences is proposed. An approach to choosing a "biologically correct" alignment among all Pareto-optimal alignments is suggested.

• Taylor WR, Brown NP
• Iterated sequence databank search methods.
• Comput Chem. 1999; 23: 365-85
• Display abstract

• Iterated sequence databank search methods were assessed from the viewpoint of someone with the sequence of a novel gene product wishing to find distant relatives to their protein and, with the specific searches against the PDB, also hoping to find a relative of known structure. We examined three methods in detail, spanning a range from simple pattern-matching to sophisticated weighted profiles. Rather than apply these methods 'blindly' (with default parameters) to a large number of test queries, we have concentrated on the globins, so allowing a more detailed investigation of each method on different data subsets with different parameter settings. Despite their widespread use, regular-expression matching proved to be very limited-seldom extending beyond the sub-family from which the pattern was derived. To attain any generality, the patterns had to be 'stripped-down' to include only the most highly conserved parts. The QUEST program avoided these problems by introducing a more flexible (weighted) matching. On the PDB sequences this was highly effective, missing only a few globins with probes based on each sub-family or even a single representative from each sub-family. In addition, very few false-positives were encountered, and those that did match, often only did so for a few cycles before being lost again. On the larger sequence collection, however, QUEST encountered problems with maintaining (or achieving) the alignment of the full globin family. psi-BLAST also recognised almost all the globins when matching against the PDB sequences, typically, missing three or four of the most distantly related sequences while picking-up a few false-positives. In contrast to QUEST, psi-BLAST performed very well on the larger databank, getting almost a full collection of globins although still retaining the same proportion of false-positives. SAM applied to the PDB sequences performed reasonably well with the myoglobin and hemoglobin families as probes, missing, typically several of the more difficult proteins but performed poorly with the leghemoglobin probe. Only with the full family range as a probe did it produce results comparable to psi-BLAST and QUEST. With the larger databank, SAM produced a good result but, again, this was only achieved using the full range of sequence variation with the default regulariser and use of Dirichlet mixtures completely failed in this situation.

• Yuan J et al.
• MULTICLUSTAL: a systematic method for surveying Clustal W alignment parameters.
• Bioinformatics. 1999; 15: 862-3
• Display abstract

• MULTICLUSTAL is a Perl script designed to automate the process of alignment parameter choice for Clustal W with the goal of generating high quality multiple sequence alignments.

• Maras B, Barra D, Dupre S, Pitari G
• Is pantetheinase the actual identity of mouse and human vanin-1 proteins?
• FEBS Lett. 1999; 461: 149-52
• Display abstract

• Pantetheinase is an amidohydrolase involved in the dissimilative pathway of CoA, allowing the turnover of the pantothenate moiety. We have determined the N-terminal sequence as well as the sequences of a number of tryptic and chymotryptic peptides of the protein isolated from pig kidney. These sequence stretches were used as probes to search in the SwissProt database and significant similarities were found with a GPI-anchored protein (mouse vanin-1, with a suggested role in lymphocyte migration), with two putative proteins encoded by human cDNAs (VNN1 and VNN2) and with human biotinidase. On the basis of sequence similarity, we propose that vanin-1 and VNN1 should be identified as pantetheinase.

• Gomes CM, Teixeira M
• Ambineela, an unusual blue protein isolated from the archaeon Acidianus ambivalens.
• Biochem Biophys Res Commun. 1998; 249: 23-5
• Display abstract

• A novel blue protein, named ambineela, was isolated from the soluble extract of the thermoacidophilic archaeon Acidianus ambivalens. In solution, the purified protein is a monomer with 50 kDa and has a basic character (pI approximately 8.7). The electronic spectrum shows two bands, centred at 395 and 625 nm (A625/A395 = 0.7). The protein does not contain any transition metal; its blue colour is due to an unidentified non-fluorescent cofactor, covalently bound to it. Ambineela N-terminal sequence exhibits a consensus ADP-binding region, suggesting that its unknown cofactor may comprise this molecule or an analogue.

• Aguiari G et al.
• K562 erythroid and HL60 macrophage differentiation downregulates polycystin, a large membrane-associated protein.
• Exp Cell Res. 1998; 244: 259-67
• Display abstract

• Polycystin, the PKD1 gene product mutated in autosomal dominant polycystic kidney disease, is a large membrane protein which is important in the differentiation of epithelial tubular structure. Furthermore, PKD1 mRNA is expressed in various tissues and in neoplastic cell lines particularly, suggesting that polycystin might be involved in differentiation and/or proliferation of other cell types. Therefore, in order to investigate such a possible role, polyclonal antibodies against a recombinant polycystin peptide were raised and used to study polycystin expression in human leukemia cell lines committed to differentiation. Using Western blot and laser scanning confocal microscopy analyses, we demonstrated expression of polycystin in erythroleukemia K562 cells as a membrane-associated polypeptide of approximately 450 kDa, mainly localized in cell-cell contacts. Protein size and subcellular distribution were similar to those found in the kidney epithelial KJ29 cell line. In addition, K562 cell erythroid differentiation induced by hemin was characterized by a reduction in polycystin expression, as measured by Western blot and Northern blot analyses. Cytofluorimetric analysis indicated that upon hemin treatment there was a progressive reduction in the number of polycystin-expressing cells as well as in proliferation rate. Furthermore, reduction in proliferating and polycystin-expressing cells was also observed in K562 cells after serum starvation. When serum was added to the serum-deprived cells an increase in cell number as well as in number of polycystin-positive cells was observed. In addition, polycystin, also expressed in promyelocytic leukemia HL60 cells, was downregulated when macrophage differentiation in HL60 was induced by TPA. Therefore, in these leukemic cells downregulation of polycystin appeared to be closely related to reduction in cell proliferation and to induction of differentiation. This suggests that polycystin may play a relevant role in these cell processes.

• Janecek S, Zamocky M, Koller F
• Indication of a common ancestry for copper tyrosinases and heme catalases revealed by hydrophobic cluster analysis of the brown locus protein sequence.
• Protein Eng. 1998; 11: 501-4

• Escalier V, Pothier J, Soldano H, Viari A
• Pairwise and multiple identification of three-dimensional common substructures in proteins.
• J Comput Biol. 1998; 5: 41-56
• Display abstract

• In this paper, we present an algorithm to find three-dimensional substructures common to two or more molecules. The basic algorithm is devoted to pairwise structural comparison. Given two sets of atomic coordinates, it finds the largest subsets of atoms which are "similar" in the sense that all internal distances are approximately conserved. The basic idea of the algorithm is to recursively build subsets of increasing sizes, combining two sets of size k to build a set of size k + 1. The algorithm can be used "as is" for small molecules or local parts of proteins (about 30 atoms). When a high number of atoms is involved, we use a two step procedure. First we look for common "local" fragments by using the previous algorithm, and then we gather these fragments by using a Branch and Bound technique. We also extend the basic algorithm to perform multiple comparisons, by using one of the structures as a reference point (pivot) to which all other structures are compared. The solution is the largest subsets of atoms common to the pivot and at least q other structures. Although both algorithms are theoretically exponential in the number of atoms, experiments performed on biological data and using realistic parameters show that the solution is obtained within a few minutes. Finally, an application to the determination of the structural core of seven globins is presented.

• Pirkle H
• Thrombin-like enzymes from snake venoms: an updated inventory. Scientific and Standardization Committee's Registry of Exogenous Hemostatic Factors.
• Thromb Haemost. 1998; 79: 675-83

• Gary JD, Clarke S
• RNA and protein interactions modulated by protein arginine methylation.
• Prog Nucleic Acid Res Mol Biol. 1998; 61: 65-131
• Display abstract

• This review summarizes the current status of protein arginine N-methylation reactions. These covalent modifications of proteins are now recognized in a number of eukaryotic proteins and their functional significance is beginning to be understood. Genes that encode those methyltransferases specific for catalyzing the formation of asymmetric dimethylarginine have been identified. The enzyme modifies a number of generally nuclear or nucleolar proteins that interact with nucleic acids, particularly RNA. Postulated roles for these reactions include signal transduction, nuclear transport, or a direct modulation of nucleic acid interactions. A second methyltransferase activity that symmetrically dimethylates an arginine residue in myelin basic protein, a major component of the axon sheath, has also been characterized. However, a gene encoding this activity has not been identified to date and the cellular function for this methylation reaction has not been clearly established. From the analysis of the sequences surrounding known arginine methylation sites, we have determined consensus methyl-accepting sequences that may be useful in identifying novel substrates for these enzymes and may shed further light on their physiological role.

• Taurog A, Wall M
• Proximal and distal histidines in thyroid peroxidase: relation to the alternatively spliced form, TPO-2.
• Thyroid. 1998; 8: 185-91
• Display abstract

• The distal and proximal histidines in thyroid peroxidase (TPO), located by amino acid sequence alignment with their known counterparts in myeloperoxidase, are His 239 and His 494, respectively. These histidines lie outside the 57 amino acid peptide (residues 533-589) that is absent in the alternatively spliced form, TPO-2. However, asparagine 579, which very likely forms a stabilizing hydrogen bond with the proximal histidine in TPO, lies within the missing peptide region. The absence of Asn 579 from TPO-2 may be at least partially responsible for the reported lack of activity of this form of the enzyme. Formation of TPO compound I may also depend on Arg 396, based on analogy with the catalytic mechanism previously proposed for the more widely studied plant and fungal peroxidases. A multiple sequence alignment prepared with five mammalian and five invertebrate peroxidases shows complete conservation of Arg 396, as well as residues corresponding to His 239, His 494, and Asn 579 in TPO. The animal peroxidases comprise a family of homologous proteins that differ markedly from the plant/fungal/bacterial peroxidases in primary, secondary, and tertiary structure, yet share with them a common function. Animal peroxidases probably arose independently of the plant/fungal/bacterial peroxidase superfamily and most likely belong to a different gene family. The relation between animal and nonanimal peroxidases may represent an example of convergent evolution to a common enzymatic mechanism.

• Altschul SF
• Generalized affine gap costs for protein sequence alignment.
• Proteins. 1998; 32: 88-96
• Display abstract

• Based on the observation that a single mutational event can delete or insert multiple residues, affine gap costs for sequence alignment charge a penalty for the existence of a gap, and a further length-dependent penalty. From structural or multiple alignments of distantly related proteins, it has been observed that conserved residues frequently fall into ungapped blocks separated by relatively nonconserved regions. To take advantage of this structure, a simple generalization of affine gap costs is proposed that allows nonconserved regions to be effectively ignored. The distribution of scores from local alignments using these generalized gap costs is shown empirically to follow an extreme value distribution. Examples are presented for which generalized affine gap costs yield superior alignments from the standpoints both of statistical significance and of alignment accuracy. Guidelines for selecting generalized affine gap costs are discussed, as is their possible application to multiple alignment.

• Neuwald AF, Koonin EV
• Ataxin-2, global regulators of bacterial gene expression, and spliceosomal snRNP proteins share a conserved domain.
• J Mol Med. 1998; 76: 3-5

• Gendel SM
• The use of amino acid sequence alignments to assess potential allergenicity of proteins used in genetically modified foods.
• Adv Food Nutr Res. 1998; 42: 45-62

• Campagne F, Maigret B
• Multiple sequence alignment in HTML: colored, possibly hyperlinked, compact representations.
• J Mol Graph Model. 1998; 16: 6-10
• Display abstract

• Protein sequence alignments are widely used in protein structure prediction, protein engineering, modeling of proteins, etc. This type of representation is useful at different stages of scientific activity: looking at previous results, working on a research project, and presenting the results. There is a need to make it available through a network (intranet or WWW), in a way that allows biologists, chemists, and noncomputer specialists to look at the data and carry on research--possibly in a collaborative research. Previous methods (text-based, Java-based) are reported and their advantages are discussed. We have developed two novel approaches to represent the alignments as colored, hyper-linked HTML pages. The first method creates an HTML page that uses efficiently the image cache mechanism of a WWW browser, thereby allowing the user to browse different alignments without waiting for the images to be loaded through the network, but only for the first viewed alignment. The generated pages can be browsed with any HTML2.0-compliant browser. The second method that we propose uses W3C-CSS1-style sheets to render alignments. This new method generates pages that require recent browsers to be viewed. We implemented these methods in the Viseur program and made a WWW service available that allows a user to convert an MSF alignment file in HTML for WWW publishing. The latter service is available at http:@www.lctn.u-nancy.fr/viseur/services.htm l.

• Gerstein M, Levitt M
• Comprehensive assessment of automatic structural alignment against a manual standard, the scop classification of proteins.
• Protein Sci. 1998; 7: 445-56
• Display abstract

• We apply a simple method for aligning protein sequences on the basis of a 3D structure, on a large scale, to the proteins in the scop classification of fold families. This allows us to assess, understand, and improve our automatic method against an objective, manually derived standard, a type of comprehensive evaluation that has not yet been possible for other structural alignment algorithms. Our basic approach directly matches the backbones of two structures, using repeated cycles of dynamic programming and least-squares fitting to determine an alignment minimizing coordinate difference. Because of simplicity, our method can be readily modified to take into account additional features of protein structure such as the orientation of side chains or the location-dependent cost of opening a gap. Our basic method, augmented by such modifications, can find reasonable alignments for all but 1.5% of the known structural similarities in scop, i.e., all but 32 of the 2,107 superfamily pairs. We discuss the specific protein structural features that make these 32 pairs so difficult to align and show how our procedure effectively partitions the relationships in scop into different categories, depending on what aspects of protein structure are involved (e.g., depending on whether or not consideration of side-chain orientation is necessary for proper alignment). We also show how our pairwise alignment procedure can be extended to generate a multiple alignment for a group of related structures. We have compared these alignments in detail with corresponding manual ones culled from the literature. We find good agreement (to within 95% for the core regions), and detailed comparison highlights how particular protein structural features (such as certain strands) are problematical to align, giving somewhat ambiguous results. With these improvements and systematic tests, our procedure should be useful for the development of scop and the future classification of protein folds.

• Nakamura Y
• [Protein-RNA molecular mimicry]
• Tanpakushitsu Kakusan Koso. 1998; 43: 1421-32

• Mian IS, Moser MJ
• The Fanconi anemia complementation group A protein contains a peroxidase domain.
• Mol Genet Metab. 1998; 63: 230-4
• Display abstract

• Computational analysis of the Fanconi anemia (FA) complementation group A protein suggests that it contains a peroxidase domain. FA proteins may be part of a general mechanism that protects cells from oxidative damage.

• Bruce LJ, Unwin RJ, Wrong O, Tanner MJ
• The association between familial distal renal tubular acidosis and mutations in the red cell anion exchanger (band 3, AE1) gene.
• Biochem Cell Biol. 1998; 76: 723-8
• Display abstract

• In distal renal tubular acidosis (dRTA) the tubular secretion of hydrogen ion in the distal nephron is impaired, leading to the development of metabolic acidosis, frequently accompanied by hypokalemia, nephrocalcinosis, and metabolic bone disease. The condition can be familial, when it is usually inherited as an autosomal dominant, though there is a rarer autosomal recessive form associated with nerve deafness. It has been shown that the autosomal dominant form of dRTA is associated with a defect in the anion exchanger (AE1) of the renal collecting duct intercalated cell. This transporter is a product of the same gene (AE1) as the erythrocyte anion exchanger, band 3. In this review we will look at the evidence for this association. Studies of genomic DNA from families with this disorder have shown, both by genetic linkage studies and by DNA sequencing, that affected individuals are heterozygous for mutations in the AE1 gene whilst unaffected family members have a normal band 3 sequence. Mutations have been found in the region of proposed helices 6 and 7 of the membrane domain of band 3 and involve amino acids Arg-589 and Ser-613, and in the COOH-terminal domain of band 3. Studies of red cell band 3 from these families have provided information on the effect these mutations have on the structure and function of erythrocyte band 3. Expression studies of the erythroid and kidney isoforms of the mutant AE1 proteins, in Xenopus laevis oocytes, have shown that they retained chloride transport activity, suggesting that the disease in the dRTA families is not related simply to the anion transport activity of the mutated proteins. A possible explanation for the dominant effect of these mutant AE1 proteins in the kidney cell is that these mutations affect the targeting of AE1 from the basolateral to the apical membrane of the alpha-intercalated cell.

• Zamiatnin AA, Voronina OL
• [Common physicochemical characteristics of endogenous hormones-- liberins and statins]
• Biofizika. 1998; 43: 438-46
• Display abstract

• The common chemical features of oligopeptide releasing-hormones and release inhibiting hormones were investigated with the aid of computer methods. 339 regulatory molecules of such type have been extracted out of data from computer bank EROP-Moscow. They contain from 2 to 47 amino acid residues and their sequences include short sites, which play apparently a decisive role in realization of interactions with the receptors. The analysis of chemical radicals shows that all liberins and statins contain positively charged group and cyclic radical of some amino acids or hydrophobic group. Results of this study indicate that the most chemical radicals of hormones are open for the interaction with potential receptors of target-cells. The mechanism of hormone ligand and receptors binding and conceivable role of amino acid and neurotransmitter radicals in hormonal properties of liberins and statins is discussed.

• Andreeva SG et al.
• [Study of structure of secretory 28 kDa protein from the rat olfactory epithelium]
• Bioorg Khim. 1998; 24: 816-21
• Display abstract

• Clone lambda a26.1 isolated from rat olfactory epithelium contains a full-length 28-kDa protein cDNA (1414 b.p.). The reconstructed protein sequence comprises 223 aa with a calculated molecular mass of 24,630 Da. A substantial homology was revealed between the amino acid sequence of the 28-kDa protein and those of thiol-specific antioxidants (peroxiredoxines). The 28-kDa protein belongs to the 1 Cys-subfamily of peroxiredoxines and is the first member of peroxiredoxines identified in the olfactory epithelium.

• von dem Borne AE et al.
• Thrombopoietin and its receptor: structure, function and role in the regulation of platelet production.
• Baillieres Clin Haematol. 1998; 11: 409-26

• Baker DJ, Gore MG
• A chaperonin apical domain from the thermophilic bacterium Thermus Aquaticus.
• Biochem Soc Trans. 1998; 26: 250-250

• Restani P, Fiocchi A, Beretta B, Velona T, Giovannini M, Galli CL
• Effects of structure modifications on IgE binding properties of serum albumins.
• Int Arch Allergy Immunol. 1998; 117: 113-9
• Display abstract

• BACKGROUND: Bovine serum albumin (BSA) is one of the most widely studied proteins; its structure is well-known and its antigenic characteristics have been described in studies performed in in vitro and animal models. The aim of our work was to evaluate the role of BSA conformation in its antigenicity (recognition by circulating IgEs from allergic children). METHODS: This study was performed using electrophoresis associated with the immunoblotting technique, where sera from children sensitized to BSA (as shown by double-blind placebo-controlled food challenge) were used. RESULTS AND DISCUSSION: Heat treatment and chemical denaturation (SDS treatment) are not able to decrease the BSA capability to bind circulating IgEs. Only by reducing treatment with 2-mercaptoethanol is it possible to modify but not to eliminate the antigenicity of this protein. The reactivity to other serum albumins from different animal species was also investigated and in this study we show a direct correlation between the number of IgE-mediated responses observed in immunoblotting and the percentage of sequence identity (phylogenetic similarity) of serum albumins. CONCLUSION: Data obtained in this research indicate that serum albumin antigenicity is only partially correlated to its native three-dimensional structure.

• De Caro J, Carriere F, Barboni P, Giller T, Verger R, De Caro A
• Pancreatic lipase-related protein 1 (PLRP1) is present in the pancreatic juice of several species.
• Biochim Biophys Acta. 1998; 1387: 331-41
• Display abstract

• Pancreatic lipase-related protein 1 (PLRP1) was purified from human, canine, porcine and rat pancreatic juices. The four PLRP1s were identified using microsequencing methods after performing gel filtration on Ultrogel AcA-54 followed by chromatography on Heparin-Sepharose cation-exchanger. Polyclonal antibodies specific to human PLRP1 (HPLRP1) were raised in the rabbit using a synthetic decapeptide from HPLRP1. The results of Western blotting analysis showed that these antibodies recognized native HPLRP1 and recombinant HPLRP1 produced by insect cells, and cross-reacted only with rat PLRP1 (RPLRP1). No significant lipolytic activity was observed with native canine PLRP1 and recombinant HPLRP1 on various glycerides, phospholipid and vitamin esters, or on cholesterol esters. It was established for the first time that this protein is secreted in variable amounts by the adult exocrine pancreas of several species.

• Ong AC, Harris PC
• Molecular basis of renal cyst formation--one hit or two?
• Lancet. 1997; 349: 1039-40

• Krieger J, Mameli M, Breer H
• Elements of the olfactory signaling pathways in insect antennae.
• Invert Neurosci. 1997; 3: 137-44
• Display abstract

• Owing to their enormous ability to recognize airborne molecules, insects have long been used as model systems for studying various aspects of olfaction. Modern biological techniques have opened new avenues for exploring the molecular mechanisms underlying the complex signaling processes in chemosensory neurons. Biochemical and molecular analyses have allowed the identification of molecular elements of the olfactory reaction pathways and have shed light on mechanisms that account for the sensitivity and specificity of the chemosensory system.

• Taylor WR
• Residual colours: a proposal for aminochromography.
• Protein Eng. 1997; 10: 743-6

• Weston BS et al.
• Polycystin expression during embryonic development of human kidney in adult tissues and ADPKD tissue.
• Histochem J. 1997; 29: 847-56
• Display abstract

• Normal renal tissue, ranging from 8 weeks' gestation to full term to adult, was probed with polyclonal antibodies raised to peptide epitopes within the translated PKD1 gene sequence. Three antibodies were studied, all of which gave similar results. Renal tissue from patients with autosomal dominant polycystic kidney disease (ADPKD) and samples from normal adult liver, heart, brain, skeletal muscle and lymph node were also studied. Tissue staining demonstrated that the pattern of polycystin expression changed with gestational age in normal kidney. Whereas the precursors to the renal excretory unit were stained at 12 weeks, and the proximal and distal convoluted tubules stained to differing degrees throughout development, the glomeruli were poorly stained until full term and also in the adult. Extrarenal tissue stained in both adult and juvenile samples, with the exception of lymph node, which remained unstained. The intensity of polycystin staining increased in ADPKD renal tissue. The widespread distribution of polycystin was consistent with the systemic nature of ADPKD and the role of epithelial cells in the disease.

• Henry J, Ribouchon MT, Offer C, Pontarotti P
• B30.2-like domain proteins: a growing family.
• Biochem Biophys Res Commun. 1997; 235: 162-5
• Display abstract

• The B30.2 domain is a conserved domain of around 170 amino acids. It is found associated with different protein domains: immunoglobulin domain in the case of butyrophilin and Ring Finger domain in the case of Ret Finger Protein. B30.2 should therefore be considered a migratory domain. We here report new members of these families as well as new protein families having the B30.2 domain, and we tentatively propose a general function for this domain.

• Geng L et al.
• Distribution and developmentally regulated expression of murine polycystin.
• Am J Physiol. 1997; 272: 4519-4519
• Display abstract

• PKD1, the gene that is mutated in approximately 85% of autosomal dominant polycystic kidney disease (ADPKD) cases in humans, has recently been identified (Eur. PKD Consortium. Cell 77: 881-894, 1994; also, erratum in Cell 78: 1994). The longest open-reading frame of PKD1 encodes polycystin, a novel approximately 460-kDa protein that contains a series of NH2-terminal adhesive domains (J. Hughes, C. J. Ward, B. Peral, R. Aspinwall, K. Clark, J. San Millan, V. Gamble, and P. C. Harris. Nat. Genet. 10: 151-160, 1995; and Int. PKD Consortium. Cell 81: 289-298, 1995) and several putative transmembrane segments. To extend studies of polycystin to an experimentally accessible animal, we have isolated a cDNA clone encoding the 3' end of Pkd1, the mouse homologue of PKD1, and raised a specific antibody to recombinant murine polycystin. This antibody was used to determine the subcellular localization and tissue distribution of the protein by Western analysis and immunocytochemistry. In the mouse, polycystin is an approximately 400-kDa molecule that is predominantly found in membrane fractions of tissue and cell extracts. It is expressed in many tissues including kidney, liver, pancreas, heart, intestine, lung, and brain. Renal expression, which is confined to tubular epithelia, is highest in late fetal and early neonatal life and drops 20-fold by the third postnatal week, maintaining this level into adulthood. Thus the temporal profile of polycystin expression coincides with kidney tubule differentiation and maturation.

• Hoffman DR
• Hymenoptera venom proteins.
• Adv Exp Med Biol. 1996; 391: 169-86

• Al-Awqati Q
• Puzzling polycystin.
• Mol Med. 1996; 2: 663-4

• Urade Y, Watanabe K, Hayaishi O
• Prostaglandin D, E, and F synthases.
• J Lipid Mediat Cell Signal. 1995; 12: 257-73

• Nishikawa K
• [Prediction of protein structures]
• Tanpakushitsu Kakusan Koso. 1992; 37: 592-9

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