Lipid-binding serum glycoprotein

Last updated
LBP / BPI / CETP family, N-terminal domain
PDB 1bp1 EBI.jpg
crystal structure of bpi, the human bactericidal permeability-increasing protein
Identifiers
SymbolLBP_BPI_CETP
Pfam PF01273
InterPro IPR017942
PROSITE PDOC00367
SCOP2 1bp1 / SCOPe / SUPFAM
TCDB 1.C.40
OPM superfamily 170
OPM protein 2obd
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
LBP / BPI / CETP family, C-terminal domain
PDB 1bp1 EBI.jpg
crystal structure of bpi, the human bactericidal permeability-increasing protein
Identifiers
SymbolLBP_BPI_CETP_C
Pfam PF02886
InterPro IPR001124
PROSITE PDOC00367
SCOP2 1bp1 / SCOPe / SUPFAM
TCDB 1.C.40
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

In molecular biology, the lipid-binding serum glycoproteins family, also known as the BPI/LBP/Plunc family or LBP/BPI/CETP family represents a family which includes mammalian lipid-binding serum glycoproteins and/or proteins containing a structural motif known as the BPI fold. Members of this family include:

Contents

Structure

These proteins consist of N- and C-terminal domains, which share a similar two-layer alpha/beta structure, but show little sequence identity to each other. These domains were first described as being arranged in a "boomerang" shape that creates the BPI fold. [4] The fold contains apolar binding pockets that can interact with hydrophobic and amphipathic molecules, such as the acyl carbon chains of lipopolysaccharide found on Gram-negative bacteria.

Function

Bactericidal permeability-increasing protein

Bactericidal permeability-increasing protein (BPI) is a potent antimicrobial protein of 456 amino acids that binds to and neutralises lipopolysaccharides from the outer membrane of Gram-negative bacteria. [5] BPI contains two domains that adopt the same structural fold, even though they have little sequence similarity. [6]

Lipopolysaccharide-binding protein

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. [7]

Cholesteryl ester transfer protein

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. [8]

Phospholipid transfer protein

Phospholipid transfer protein (PLTP) exchanges phospholipids between lipoproteins and remodels high-density lipoproteins (HDLs). [9]

Palate, lung and nasal epithelium carcinoma-associated protein

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. [10]

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. [11]

Bacterial permeability family member A1 (BPIFA1/SPLUNC1) is an innate protein that is secreted basolaterally from healthy, but not asthmatic, human bronchial epithelial cultures (HBECs). It suppresses airway smooth muscle contractility by binding to and inhibiting the Ca2+ influx channel Orai1. [12]

Human proteins belonging to this family

Related Research Articles

Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. VLDL is assembled in the liver from triglycerides, cholesterol, and apolipoproteins. VLDL is converted in the bloodstream to low-density lipoprotein (LDL) and intermediate-density lipoprotein (IDL). VLDL particles have a diameter of 30–80 nm. VLDL transports endogenous products, whereas chylomicrons transport exogenous (dietary) products. In the early 2010s both the lipid composition and protein composition of this lipoprotein were characterised in great detail.

<span class="mw-page-title-main">Chylomicron</span> One of the five major groups of lipoprotein

Chylomicrons, also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), phospholipids (6–12%), cholesterol (1–3%), and proteins (1–2%). They transport dietary lipids from the intestines to other locations in the body. ULDLs are one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. A protein specific to chylomicrons is ApoB48.

<span class="mw-page-title-main">Torcetrapib</span> Chemical compound

Torcetrapib was a drug being developed to treat hypercholesterolemia and prevent cardiovascular disease. Its development was halted in 2006 when phase III studies showed excessive all-cause mortality in the treatment group receiving a combination of atorvastatin (Lipitor) and torcetrapib.

<span class="mw-page-title-main">Cholesteryl ester transfer protein</span> Mammalian protein found in Homo sapiens

Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It collects triglycerides from very-low-density (VLDL) or Chylomicrons and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a heteroexchange, trading a triglyceride for a cholesteryl ester or a cholesteryl ester for a triglyceride.

<span class="mw-page-title-main">CD14</span> Mammalian protein found in Homo sapiens

CD14 is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP).

Bactericidal/permeability-increasing protein (BPI) is a 456-residue (~50kDa) protein that is part of the innate immune system. It belongs to family of lipid-binding serum glycoproteins.

<span class="mw-page-title-main">Lipopolysaccharide binding protein</span> Protein in humans

Lipopolysaccharide binding protein (LBP) is a protein that in humans is encoded by the LBP gene.

<span class="mw-page-title-main">BPIFA1</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family A, member 1 (BPIFA1), also known as Palate, lung, and nasal epithelium clone (PLUNC), is a protein that in humans is encoded by the BPIFA1 gene. It was also formerly known as "Secretory protein in upper respiratory tracts" (SPURT). The BPIFA1 gene sequence predicts 4 transcripts ; 3 mRNA variants have been well characterized. The resulting BPIFA1 is a secreted protein, expressed at very high levels in mucosa of the airways and salivary glands; at high levels in oropharyneal epithelium, including tongue and tonsils; and at moderate levels many other tissue types and glands including pituitary, testis, lung, bladder, blood, prostate, pancreas, levels in the digestive tract and pancreas. The protein can be detected on the apical side of epithelial cells and in airway surface liquid, nasal mucus, and sputum.

<span class="mw-page-title-main">Phospholipid transfer protein</span> Mammalian protein found in Homo sapiens

Phospholipid transfer protein is a protein that in humans is encoded by the PLTP gene.

Sterol O-acyltransferase is an intracellular protein located in the endoplasmic reticulum that forms cholesteryl esters from cholesterol.

<span class="mw-page-title-main">BPIFB2</span> Protein-coding gene in the species Homo sapiens

BPI fold-containing family B, member 2, (BPIFB2) also known as bactericidal/permeability-increasing protein-like 1, is a protein that in humans is encoded by the BPIFB2 gene.

<span class="mw-page-title-main">BPIFA3</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family A, member 3 (BPIFA3) is a protein that in humans is encoded by the BPIFA3 gene. The gene is also known as SPLUNC3 and C20orf71 in humans and the orthologous gene in mice is 1700058C13Rik. There are multiple variants of the BPIFA3 projected to be a secreted protein. It is very highly expressed in testis with little or no expression in other tissues. The Human Protein Atlas project and Mouse ENCODE Consortium report RNA-Seq expression at RPKM levels of 29.1 for human testis and 69.4 for mouse, but 0 for all other tissues. Similarly, the Bgee consortium, using multiple techniques in addition to RNA-Seq, reports a relative Expression Score of 95.8 out of 100 for testis and 99.0 for sperm in humans; however low levels of BPIFA3 between 20-30 were seen for a variety of tissues such as muscle, glands, prostate, nervous system, and skin.

<span class="mw-page-title-main">BPIFB4</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family B, member 4 (BPIFB4) is a protein that in humans is encoded by the BPIFB4 gene. It was formerly known as "Long palate, lung and nasal epithelium carcinoma-associated protein 4" encoded by the LPLUNC4 gene. The BPIFB4 gene sequence predicts 4 transcripts ; 3 isoforms have been well characterized. In a variety of mammals, BPIFB4 is generally expressed in very high levels in the olfactory epithelium, high levels in the gonads and pituitary, moderate levels in white blood cells (monocytes) It can occur either localized in the cytoplasm of cells or secreted and circulated systemically in blood plasma.

<span class="mw-page-title-main">BPIFB1</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family B, member 1 (BPIFB1) is a protein that in humans is encoded by the BPIFB1 gene. BPIFB1 is a secreted protein, expressed at very high levels in mucosa of the airways and salivary glands, and at moderate levels in the digestive tract and pancreas.

<span class="mw-page-title-main">BPIFB3</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family B, member 3 (BPIFB3) is a protein that in humans is encoded by the BPIFB3 gene. Two variants have been detected in humans.

<span class="mw-page-title-main">BPIFB5P</span> Pseudogene in the species Homo sapiens

BPI fold containing family B, member 5 is a non-human protein encoded by the Bpifb5 gene, also known as Lplunc5. The BPIFB5 protein and Bpifb5 gene have been characterized in mammals such as rodents and even-toed ungulates but are apparently lacking in primates and other vertebrates such as birds, reptiles, and amphibians. The protein in rodents is expressed at moderately high levels in mucosa of the airways and at moderate levels in salivary glands, esophagus, and gonads ; in even-toed ungulates expression is high in testis, moderate in brain and striated muscle, and low in kidney.

<span class="mw-page-title-main">BPIFB6</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family B, member 6 (BPIFB6), also known as bactericidal/permeability-increasing protein-like 3 (BPIL3), is a protein that in humans is encoded by the BPIFB6 gene, also known as BPIL3 and LPLUNC6. It is expressed at high levels in hypertrophic tonsils, at relatively moderate levels in oronasal epithelium including nasal mucosa, tongue, and salivary gland, as well as esophageal mucosa at lesser levels. Orthologs are present in many vertebrate species including mammals, birds, reptiles, and amphibians.

<span class="mw-page-title-main">BPIFB9P</span> Pseudogene in the species Homo sapiens

Vomeromodulin is a non-human protein also known as BPI fold containing family B, member 9 (BPIFB9) in the rat encoded by the Bpifb9/RYF3 gene, and as BPI fold containing family B, member 9A (BPIFB9A) encoded by the Bpifb9a gene in the mouse. This protein has been characterized in mammals such as rodents, carnivores, even-toed ungulates, insectivores, bats, lagomorphs, and shrews but is apparently absent in primates and other vertebrates such as birds, reptiles, and amphibians. Its function is associated with detection of chemical odorant pheromone molecules.

<span class="mw-page-title-main">BPIFA2</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family A, member 2 (BPIFA2), also known as Parotid Secretory Protein (PSP), is a protein that in humans is encoded by the BPIFA2 gene. The BPIFA2 gene sequence predicts multiple transcripts ; 2 mRNA variants have been well characterized. The resulting BPIFA2 is a secreted protein, expressed at very high levels in the parotid (salivary) gland; at high levels in oropharyneal mucosa, including tongue; and at moderate levels many other tissue types and glands including mammary gland, testis, lung, bladder, blood, prostate, adrenal gland, kidney, and pancreas.

<span class="mw-page-title-main">BPIFA4P</span> Pseudogene in the species Homo sapiens

BPI fold containing family A, member 4 (BPIFA4) is a non-human protein encoded by the Bpifa4 gene in monkey and cow. It is also known as Latherin in horse, encoded by the Lath/Bpifa4 gene but somewhat divergent from the other species. Latherin/BPIFA4 is a secreted protein found in saliva and sweat.

References

  1. ↑ Gray PW, Flaggs G, Leong SR, Gumina RJ, Weiss J, Ooi CE, Elsbach P (1989). "Cloning of the cDNA of a human neutrophil bactericidal protein. Structural and functional correlations". J. Biol. Chem. 264 (16): 9505–9509. PMID   2722846.
  2. ↑ Gray PW, Leong SR, Wright SD, Schumann RR, Flaggs GW, Mathison JC, Tobias PS, Ulevitch RJ (1990). "Structure and function of lipopolysaccharide binding protein". Science. 249 (4975): 1429–1431. Bibcode:1990Sci...249.1429S. doi:10.1126/science.2402637. PMID   2402637.
  3. ↑ Grant FJ, Day JR, Albers JJ, Lofton-Day CE, Gilbert TL, Marcovina SM, Adolphson JL, O Hara PJ, Ching AF (1994). "Complete cDNA encoding human phospholipid transfer protein from human endothelial cells". J. Biol. Chem. 269 (12): 9388–9391. PMID   8132678.
  4. ↑ Beamer, LJ; Carroll, SF; Eisenberg, D (April 1998). "The BPI/LBP family of proteins: a structural analysis of conserved regions". Protein Science. 7 (4): 906–914. doi:10.1002/pro.5560070408. PMC   2143972 . PMID   9568897.
  5. ↑ Beamer LJ, Carroll SF, Eisenberg D (June 1997). "Crystal structure of human BPI and two bound phospholipids at 2.4 angstrom resolution". Science. 276 (5320): 1861–4. doi:10.1126/science.276.5320.1861. PMID   9188532.
  6. ↑ Kleiger G, Beamer LJ, Grothe R, Mallick P, Eisenberg D (June 2000). "The 1.7 A crystal structure of BPI: a study of how two dissimilar amino acid sequences can adopt the same fold". J. Mol. Biol. 299 (4): 1019–34. doi:10.1006/jmbi.2000.3805. PMID   10843855. S2CID   2392067.
  7. ↑ Weiss J (August 2003). "Bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP): structure, function and regulation in host defence against Gram-negative bacteria". Biochem. Soc. Trans. 31 (Pt 4): 785–90. doi:10.1042/bst0310785. PMID   12887306. S2CID   1155741.
  8. ↑ Hamilton JA, Deckelbaum RJ (February 2007). "Crystal structure of CETP: new hopes for raising HDL to decrease risk of cardiovascular disease?". Nat. Struct. Mol. Biol. 14 (2): 95–7. doi:10.1038/nsmb0207-95. PMID   17277799. S2CID   22193394.
  9. ↑ Ponsin G, Qu SJ, Fan HZ, Pownall HJ (April 2003). "Structural and functional determinants of human plasma phospholipid transfer protein activity as revealed by site-directed mutagenesis of charged amino acids". Biochemistry. 42 (15): 4444–51. doi:10.1021/bi027006g. PMID   12693940.
  10. ↑ Bartlett JA, Hicks BJ, Schlomann JM, Ramachandran S, Nauseef WM, McCray PB (May 2008). "PLUNC is a secreted product of neutrophil granules". J. Leukoc. Biol. 83 (5): 1201–6. doi: 10.1189/jlb.0507302 . PMID   18245229. S2CID   19196781.
  11. ↑ Zhou HD, Li GY, Yang YX, Li XL, Sheng SR, Zhang WL, Zhao J (April 2006). "Intracellular co-localization of SPLUNC1 protein with nanobacteria in nasopharyngeal carcinoma epithelia HNE1 cells depended on the bactericidal permeability increasing protein domain". Mol. Immunol. 43 (11): 1864–71. doi:10.1016/j.molimm.2005.10.021. PMID   16364440.
  12. ↑ Wu, Tongde; Huang, Julianne; Moore, Patrick J.; Little, Michael S.; Walton, William G.; Fellner, Robert C.; Alexis, Neil E.; Di, Y. Peter; Redinbo, Matthew R. (2017-02-06). "Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor". Nature Communications. 8: 14118. Bibcode:2017NatCo...814118W. doi:10.1038/ncomms14118. ISSN   2041-1723. PMC   5303822 . PMID   28165446.
  13. ↑ "Q8NFQ6 - BPIFC_HUMAN". www.uniprot.org.
  14. ↑ "Q86YQ2 - LATH_HUMAN". www.uniprot.org.
This article incorporates text from the public domain Pfam and InterPro: IPR017942
This article incorporates text from the public domain Pfam and InterPro: IPR001124
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