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-binding pocket. As
structurally important residues are conserved between BPI
and CETP, it is thought that CETP and BPI may have a similar
overall conformation. We have previously proposed a model
of CETP structure based on the binding characteristics
of anti-CETP monoclonal antibodies (mAbs). We now present
a refined epitope map of CETP that has been adapted to
a structural model of CETP that uses the atomic coordinates
of BPI. Four epitopes composed of CETP residues 215–219,
219–223, 223–227, and 444–450, respectively,
are predicted to be situated on the external surface of
the central β-sheet and a fifth epitope (residues 225–258)
on an extended linker that connects the two domains of
the molecule. Three other epitopes, residues 317–331,
360–366, and 393–410, would form part of the
putative carboxy-terminal β-barrel. The ability of
the corresponding mAbs to compete for binding to CETP is
consistent with the proximity of the respective epitopes
in the model. These results thus provide experimental evidence
that is consistent with CETP and BPI having similar surface
topologies.