InterPro domain: IPR017943

This superfamily represents a structural domain with a core structure consisting of two layers, alpha/beta. These homologous structural domains can show little sequence identity with each other. A number of mammalian lipid-binding serum glycoproteins contain one or more such structural domains, including:

• 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 [ 1 ]. BPI contains two domains that adopt the same structural fold, even though they have little sequence similarity [ 2 ].

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 [ 3 ].

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 [ 4 ].

Phospholipid transfer protein (PLTP) exchanges phospholipids between lipoproteins and remodels high-density lipoproteins (HDLs) [ 5 ].

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 [ 6 ]. 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 [ 7 ].

1. Crystal structure of human BPI and two bound phospholipids at 2.4 angstrom resolution. Science 276, 1861-4
2. 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, 1019-34
3. 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, 785-90
4. Crystal structure of CETP: new hopes for raising HDL to decrease risk of cardiovascular disease? Nat. Struct. Mol. Biol. 14, 95-7
5. Structural and functional determinants of human plasma phospholipid transfer protein activity as revealed by site-directed mutagenesis of charged amino acids. Biochemistry 42, 4444-51
6. PLUNC is a secreted product of neutrophil granules. J. Leukoc. Biol. 83, 1201-6
7. 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, 1864-71