Bactericidal permeability-increasing protein (BPI) / Lipopolysaccharide-binding protein (LBP) / Cholesteryl ester transfer protein (CETP) N-terminal domain
This entry represents the N-terminal domain found in several lipid-binding serum glycoproteins. The N- and C-terminal domains share a similar two-layer alpha/beta structure, but they show little sequence identity. Proteins containing this N-terminal domain include:
Bactericidal permeability-increasing protein (BPI)
Lipopolysaccharide-binding protein (LBP)
Cholesteryl ester transfer protein (CETP)
Phospholipid transfer protein (PLTP)
Palate, lung and nasal epithelium carcinoma-associated protein (PLUNC)
Bactericidal permeability-increasing protein (BPI) is a potent antimicrobial protein of 456 residues that binds to and neutralises lipopolysaccharides from the outer membrane of Gram-negative bacteria [ (PUBMED:9188532) ]. BPI contains two domains that adopt the same structural fold, even though they have little sequence similarity [ (PUBMED:10843855) ].
Lipopolysaccharide-binding protein (LBP) is an endotoxin-binding protein that is closely related to, and functions in a co-ordinated manner with BPI to facilitate an integrated host response to invading Gram-negative bacteria [ (PUBMED:12887306) ].
Cholesteryl ester transfer protein (CETP) is a glycoprotein that facilitates the transfer of lipids (cholesteryl esters and triglycerides) between the different lipoproteins that transport them through plasma, including HDL, LDL, VLDL and chylomicrons. These lipoproteins shield the lipids from water by encapsulating them within a coating of polar lipids and proteins [ (PUBMED:17277799) ].
Phospholipid transfer protein (PLTP) exchanges phospholipids between lipoproteins and remodels high-density lipoproteins (HDLs) [ (PUBMED:12693940) ].
Palate, lung and nasal epithelium carcinoma-associated protein (PLUNC) is a potential host defensive protein that is secreted from the submucosal gland to the saliva and nasal lavage fluid. PLUNC appears to be a secreted product of neutrophil granules that participates in an aspect of the inflammatory response that contributes to host defence [ (PUBMED:18245229) ]. Short palate, lung and nasal epithelium clone 1 (SPLUNC1) may bind the lipopolysaccharide of Gram-negative nanobacteria, thereby playing an important role in the host defence of nasopharyngeal epithelium [ (PUBMED:16364440) ].
Structure and function of the plasma phospholipid transfer protein.
Curr Opin Lipidol. 1998; 9: 203-9
Display abstract
Recent cloning and sequencing of plasma phospholipid transfer protein complementary DNA revealed that phospholipid transfer protein belongs to the lipid transfer/lipopolysaccharide binding protein family that includes the cholesteryl ester transfer protein, the bactericidal permeability increasing protein and the lipopolysaccharide-binding protein. In addition to structural similarities, members of the lipid transfer/lipopolysaccharide-binding protein family might share some common functional properties, and recent studies demonstrated that phospholipid transfer protein can act in several distinct metabolic processes. In particular, the molecular transfer of phospholipids, unesterified cholesterol, alpha-tocopherol and lipopolysaccharides by phospholipid transfer protein suggests that it might be involved both in lipoprotein metabolism and in antimicrobial defence, resulting in a growing interest in this protein.
The genomic organization of the genes for human lipopolysaccharide binding protein (LBP) and bactericidal permeability increasing protein (BPI) is highly conserved.
Biochem Biophys Res Commun. 1997; 236: 427-30
Display abstract
We have determined the exon/intron organization of the human lipopolysaccharide binding protein (LBP) and bactericidal permeability increasing protein (BPI) genes. The LBP gene spans approximately 28.5 kb and is composed of 14 exons while the 31.5-kb-long BPI gene is composed of 15 exons. Comparison of the genomic organization of the LBP and BPI genes together with the genomic structures of the PLTP (phospholipid transfer protein) and CETP (cholesteryl ester transfer protein) genes, which all together constitute a gene family of functionally related proteins, revealed high homology with a remarkable conservation of exon/intron transitions. The exon/intron junctions of the LBP, BPI, and PLTP genes are almost identical, with most of the exons being of the same size. In addition, functional domains are conserved in these proteins. The C-terminal octapeptide important for CETP anchoring in lipoprotein particles is also present in LBP, BPI, and PLTP. The LPS binding motif in exons 3 and 4 has been retained in LBP and BPI. Our results indicate that the LBP, BPI, and PLTP genes, and probably the CETP gene, may have evolved from a common primordial gene and may share similar functional properties.
Structure and function of lipopolysaccharide binding protein.
Science. 1990; 249: 1429-31
Display abstract
The primary structure of lipopolysaccharide binding protein (LBP), a trace plasma protein that binds to the lipid A moiety of bacterial lipopolysaccharides (LPSs), was deduced by sequencing cloned complementary DNA. LBP shares sequence identity with another LPS binding protein found in granulocytes, bactericidal/permeability-increasing protein, and with cholesterol ester transport protein of the plasma. LBP may control the response to LPS under physiologic conditions by forming high-affinity complexes with LPS that bind to monocytes and macrophages, which then secrete tumor necrosis factor. The identification of this pathway for LPS-induced monocyte stimulation may aid in the development of treatments for diseases in which Gram-negative sepsis or endotoxemia are involved.
Cloning of the cDNA of a human neutrophil bactericidal protein. Structural and functional correlations.
J Biol Chem. 1989; 264: 9505-9
Display abstract
The bactericidal permeability increasing protein (BPI) is a 50-60-kDa membrane-associated protein isolated from granules of polymorphonuclear leukocytes. A full-length cDNA clone encoding human BPI has been isolated and the derived amino acid sequence reveals a structure that is consistent with previously determined biological properties. BPI may be organized into two domains: the amino-terminal half, previously shown to contain all known antimicrobial activity, contains a large fraction of basic and hydrophilic residues. In contrast, the carboxyl-terminal half contains more acidic than basic residues and includes several potential transmembrane regions which may anchor the holoprotein in the granule membrane. The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic aminoterminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial envelope. The amino-terminal end of BPI exhibits significant similarity with the sequence of a rabbit lipopolysaccharide-binding protein, suggesting that both molecules share a similar structure for binding lipopolysaccharides.
Metabolism (metabolic pathways involving proteins which contain this domain)
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with BPI1 domain which could be assigned to a KEGG orthologous group, and not all proteins containing BPI1 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
