Modeled on BPI's crystal structure, a proposed CETP mechanism has C-terminal residues 461-476 forming a helix that gates lipid entry into a hydrophobic pocket (Curr Opin Struct Biol 1998)

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.