Secondary literature sources for the eIF5C domain

For each of the hand selected primary papers associated with the eIF5C domain, 100 neighbouring papers are retrieved from PubMed. If one of these neighbouring papers is referenced by more than two primary papers, it is shown in the table below.

NBP35 encodes an essential and evolutionary conserved protein inSaccharomyces cerevisiae with homology to a superfamily of bacterialATPases.

Vitale G, Fabre E, Hurt EC
Gene. 1996; 178: 97-106

We have cloned a novel and essential gene, NBP35, from Saccharomycescerevisiae that encodes a putative Nucleotide Binding Protein of 35 kDa.Sequence analysis revealed structural homology of Nbp35p with a family ofbacterial ATPases involved in cell division processes and chromosomepartitioning. A search in databases identified closely related sequencesfrom yeast and higher eukaryotes, suggesting a conserved function for thisfamily of proteins. By indirect immunofluorescence, a tagged version ofNbp35p carrying two immunoglobulin G-binding domains derived fromStaphylococcus aureus Protein A was localised to the nucleus. A singleamino-acid substitution in the conserved nucleotide-binding motif ofNbp35p renders the protein non-functional. Furthermore, a conservedcluster of four cysteines in the N-terminal end of the protein is alsorequired for an essential role of Nbp35p.

Hydrophobic zippers and hook-and-eye: evolutionarily conserved proteinsequence motifs in eukaryotic acidic ribosomal proteins which are assumedto be involved in the association of the protein family.

Tsurugi K
Protein Seq Data Anal. 1992; 5: 33-8

The acidic ribosomal protein family of eukaryotic cells is thought to forma complex on ribosomes mainly by hydrophobic forces. To investigate thestructural basis of how they associate with one another, the primarysequences of the related proteins accumulated from various organisms wereanalyzed searching for evolutionarily conserved hydrophobic motifs.Initially it is shown that all the P1-type 13-kDa proteins contain abilateral hydrophobic zipper on a putative alpha-helix, which consists oftwo periodic arrays of hydrophobic amino acid residues arranged on theopposite sides of an alpha-helix. The P2-type 13-kDa proteins, except forthose from the yeast Saccharomyces cerevisiae, are shown to contain twokinds of hydrophobic areas on putative alpha-helices, which can stericallybind to each other in a hook-and-eye fashion. On the other hand, the38-kDa proteins contain a hydrophobic zipper and a hydrophobic hook indifferent helical regions. Thus, it is proposed that the 13-kDa proteinsassociate with the 38-kDa proteins via the hydrophobic zipper orhydrophobic hook-and-eye, and associate with one another with thesehydrophobic elements.

The guanine nucleotide-exchange factor, eIF-2B.

Price N, Proud C
Biochimie. 1994; 76: 748-60

Eukaryotic initiation factor eIF-2B catalyses the exchange of guaninenucleotides on another translation initiation factor, eIF-2, which itselfmediates the binding of the initiator Met-tRNA to the 40S ribosomalsubunit during translation initiation. eIF-2B promotes the release of GDPfrom inactive [eIF-2.GDP] complexes, thus allowing formation of the active[eIF-2.GTP] species which subsequently binds the Met-tRNA. This guaninenucleotide-exchange step, and thus eIF-2B activity, are known to be animportant control point for translation initiation. The activity of eIF-2Bcan be modulated in several ways. The best characterised of these involvesthe phosphorylation of the alpha-subunit of eIF-2 by specific proteinkinases regulated by particular ligands. Phosphorylation of eIF-2 alphaleads to inhibition of eIF-2B. This mechanism is involved in the controlof translation under a variety of conditions, including amino aciddeprivation in yeast (Saccharomyces cerevisiae) where it causestranslational upregulation of the transcription factor GCN4, and invirus-infected animal cells, where it involves a protein kinase activatedby double-stranded RNA. There is now also growing evidence for directregulation of eIF-2B. This appears likely to involve the phosphorylationof its largest subunit. Under certain circumstances eIF-2B may also beregulated by allosteric mechanisms. eIF-2B is a heteropentamer (subunitstermed alpha, beta, gamma, delta and epsilon) and is thus more complexthan most other guanine nucleotide-exchange factors. The genes encodingall five subunits have been cloned in yeast (exploiting the GCN4regulatory system): all but the alpha appear to be essential for eIF-2Bactivity. However, this subunit may confer sensitivity to eIF-2 alphaphosphorylation. cDNAs encoding the alpha, beta, delta and epsilonsubunits have been cloned from mammalian sources. There is substantialhomology between the yeast and mammalian sequences. Attention is nowdirected towards understanding the roles of individual subunits in thefunction and regulation of eIF-2B.

Crystal structure of the alpha subunit of human translation initiationfactor 2B.

Hiyama TB, Ito T, Imataka H, Yokoyama S
J Mol Biol. 2009; 392: 937-51

Eukaryotic translation initiation factor 2B (eIF2B) is theheteropentameric guanine-nucleotide exchange factor specific foreukaryotic initiation factor 2 (eIF2). Under stressed conditions,guanine-nucleotide exchange is strongly inhibited by the tight binding ofphosphorylated eIF2 to eIF2B. Here, we report the crystal structure of thealpha subunit of human eIF2B at 2.65 A resolution. The eIF2Balphastructure consists of the N-terminal alpha-helical domain and theC-terminal Rossmann-fold-like domain. A positively charged pocket, whoseentrance is about 15-17 A in diameter, resides at the boundary between thetwo domains. A sulfate ion is located at the bottom of the pocket (about16 A in depth). The residues comprising the sulfate-ion-binding site arestrictly conserved in eIF2Balpha. Since this deep, wide pocket with thesulfate-ion-binding site is not conserved in distant homologues, including5-methylthioribose 1-phosphate isomerases, these characteristics may bedistinctive of eIF2Balpha. Interestingly, the yeast eIF2Balpha missensemutations that reduce the eIF2B sensitivity to phosphorylated eIF2 aremapped on the other side of the pocket. One of the three human eIF2Balphamissense mutations that induce the lethal brain disorder vanishing whitematter or childhood ataxia with central nervous system hypomyelination ismapped inside the pocket. The beta and delta subunits of eIF2B arehomologous to eIF2Balpha and may have tertiary structures similar to thepresent eIF2Balpha structure. The sulfate-ion-binding residues ofeIF2Balpha are well conserved in eIF2Bbeta/delta. The abovementioned yeastand human missense mutations of eIF2Bbeta/delta were also mapped on theeIF2Balpha structure, which revealed that the human mutations areclustered on the same side as the pocket, while the yeast mutations resideon the opposite side. As most of the mutated residues are exposed on thesurface of the eIF2B subunit structure, these exposed residues are likelyto be involved in either the subunit interactions or the interaction witheIF2.