title: The implications of the structure of the bactericidal/permeability-increasing protein on the lipid-transfer function of the cholesteryl ester transfer protein.
abstract: The cholesteryl ester transfer protein (CETP) is evolutionarily related to the bactericidal/permeability-increasing protein (BPI). The recently solved structure of BPI shows an elongated, boomerang-shaped molecule, with two hydrophobic pockets opening to its concave side. These pockets each contain a phospholipid molecule. A model of CETP, based on the recently solved crystal structure of BPI, provides the basis for interpreting functional studies on CETP. In this model, C-terminal residues 461-476, which were shown to be required for neutral lipid transfer between plasma lipoproteins, from an amphipathic helix covering the opening of the N-terminal pocket. A possible lipid-transfer mechanism for CETP, with the initial step involving the disordering of lipids in the lipoprotein surface, followed by the flipping and entry of a lipid molecule into the hydrophobic lipid-binding pocket, is hypothesized in light of structural evidence and recent studies.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA. cb34@columbia.edu
authors.forename: C
authors.initials: C
authors.lastname: Bruce
authors.forename: L J
authors.initials: LJ
authors.lastname: Beamer
authors.forename: A R
authors.initials: AR
authors.lastname: Tall
mesh_terms: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008074:Lipoproteins; C053368:cationic antimicrobial protein 57, human