Immunochemical evidence that cholesteryl ester transfer protein and bactericidal/permeability-increasing protein share a similar tertiary structure

Cholesteryl ester transfer protein (CETP) plays an important role in plasma Lipoprotein metabolism through its ability to transfer cholesteryl ester, triglyceride, and phospholipid between lipoproteins. CETP is a member of a gene family that also includes bactericidal/permeability-increasing protein (BPI). The crystal structure of BPI shows it to be composed of two domains that share a similar structural fold that includes an apolar ligand-bindin g pocket. As structurally important residues are conserved between BPI and CETP, it is thought that CETP and BPI may have a similar overall conformati on. We have previously proposed a model of CETP structure based on the bind ing characteristics of anti-CETP monoclonal antibodies (mAbs). We now prese nt a refined epitope map of CETP that has been adapted to a structural mode l of CETP that uses the atomic coordinates of BPI. Four epitopes composed o f CETP residues 215-219, 219-223, 223-227, and 444-450, respectively, are p redicted to be situated on the external surface of the central beta-sheet a nd a fifth epitope (residues 225-258) on an extended linker that connects t he two domains of the molecule. Three other epitopes, residues 317-331, 360 -366, and 393-410, would form part of the putative carboxyterminal beta-bar rel. The ability of the corresponding mAbs to compete for binding to CETP i s consistent with the proximity of the respective epitopes in the model. Th ese results thus provide experimental evidence that is consistent with CETP and BPI having similar surface topologies.