Baculovirus-expressed CETP deletion mutants pinpoint residues Phe-Leu-Leu-Leu (454-457) as essential for lipid transfer, a motif shared with LCAT, LBP, BPI and other lipid-binding enzymes (Proc Natl Acad Sci U S A 1992)

Functional plasma cholesteryl ester transfer protein (CETP; 476 amino acids) has been expressed in baculovirus-transfected Sf9 insect cells by using a full-length cDNA derived from a human placental library. The product bound to each major plasma lipoprotein class, and it catalyzed the transfer of both cholesteryl esters and triglyceride. CETP species with overlapping deletions were generated in the carboxyl-terminal region. These mutants were defective in cholesteryl ester and triglyceride transfer. Structural and functional analysis suggests that normal lipoprotein binding and effective catalysis may require the carboxyl-terminal sequence -Phe-Leu-Leu-Leu- (residues 454-457), possibly with the involvement of other sequences in the carboxyl-terminal region. A similar sequence is contained in several other proteins whose functions involve binding nonpolar lipids, including lecithin: cholesterol acyltransferase, lipopolysaccharide-binding protein, bactericidal permeability-increasing protein, cholesterol 7 alpha-hydroxylase, cholesterol esterase, and hormone-sensitive lipase. These data suggest that a conserved neutral lipid-binding sequence may be one important factor in the activity of CETP and possibly in several other proteins of plasma and cellular lipid metabolism.