Mechanism of cholesteryl ester transfer protein inhibition by a neutralizing monoclonal antibody and mapping of the monoclonal antibody epitope.

  title={Mechanism of cholesteryl ester transfer protein inhibition by a neutralizing monoclonal antibody and mapping of the monoclonal antibody epitope.},
  author={T. Swenson and C. Hesler and M. L. Brown and E. Quinet and P. Trotta and M. Haslanger and F. C. Gaeta and Y. Marcel and R. Milne and A. Tall},
  journal={The Journal of biological chemistry},
  volume={264 24},
The plasma cholesteryl ester transfer protein (CETP, Mr 74,000) has a binding site for neutral lipid which can readily equilibrate with lipoprotein cholesteryl esters or triglycerides. Recently, a monoclonal antibody (TP2) was obtained which neutralizes the cholesteryl ester (CE) and triglyceride (TG) transfer activities of the CETP. In this report, the epitope of the inhibitory monoclonal antibody has been localized to a hydrophobic 26-amino acid sequence at the COOH terminus of CETP. The Fab… Expand
Structure-function relationships of human cholesteryl ester transfer protein: analysis using monoclonal antibodies.
Together with previous mutagenesis studies, the data suggests that a carboxy terminal neutral lipid binding domain may be in close proximity to a lipoprotein binding region within native CETP. Expand
Epitope mapping for the anti-rabbit cholesteryl ester transfer protein monoclonal antibody that selectively inhibits triglyceride transfer.
It is concluded that the limited interaction of Mab with a common lipid interaction site causes selective inhibition of the transfer of triglyceride that has presumably lower priority than cholesteryl ester for the CETP reaction. Expand
Defective Binding of Neutral Lipids by a Carboxyl-terminal Deletion Mutant of Cholesteryl Ester Transfer Protein
The studies suggest that amino acids 470-475 (forming part of a COOH-terminal amphipathic helix) are involved in CE and TG binding by CETP but are not required either for the binding of PC by CETp or the association of CETP with HDL. Expand
Role of cholesteryl ester transfer protein (CETP) in the HDL conversion process as evidenced by using anti-CETP monoclonal antibodies.
The results of the study demonstrate that CETP can mediate an HDL size conversion even in the absence of lipid transfers between HDL and other lipoprotein fractions, and constitute a supplementary argument for a multipotential role of CETP in lipid transport. Expand
Modification of the N-terminal cysteine of plasma cholesteryl ester transfer protein selectively inhibits triglyceride transfer activity.
Results demonstrate that the N-terminal cysteine residue of both human and rabbit plasma CETP is free and is likely to be involved in the construction of a critical part of the active site of CETP that can determine the selectivity of the lipid molecule for the transfer reaction. Expand
Description of the torcetrapib series of cholesteryl ester transfer protein inhibitors, including mechanism of actions⃞
It is demonstrated that a series of potent cholesteryl ester transfer protein (CETP) inhibitors bind specifically to CETP with 1:1 stoichiometry and block both neutral lipid and phospholipid transfer activities. Expand
Inhibition of cholesteryl ester transfer protein by apolipoproteins, lipopolysaccharides, and cholesteryl sulfate.
It is suggested from the present studies that a variety of biomolecules that can interact with lipoproteins under natural or pathological situations have the potential to modify CETP activity, which in turn could affect normal lipoprotein composition and distribution. Expand
Molecular Mechanism of the Blockade of Plasma Cholesteryl Ester Transfer Protein by Its Physiological Inhibitor Apolipoprotein CI*
It was concluded that the inhibition of CETP activity by apo CI is in direct link with its specific electrostatic properties, and the apoCI-mediated reduction in the binding properties of lipoproteins results in weaker CETP-HDL interactions and fewer cholesteryl ester transfers. Expand
Cholesteryl ester transfer protein and its inhibitors
The structure of CETP and its mechanism of action are described, details of its regulation and nonlipid transporting functions are discussed, and the results of the large scale clinical outcome trials of small molecule CETP inhibitors are summarized. Expand
Evidence That Cynomolgus Monkey Cholesteryl Ester Transfer Protein Has Two Neutral Lipid Binding Sites (*)
The fact that cholesteryl ester transfer can be inhibited without effect on triglyceride transfer and, conversely, that triglycerideTransfer can be inhibition without effect in vivo indicates that these two lipids are not transferred by a single, non-discriminatory process. Expand