HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation.
Autor: | Zhang M; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Charles R; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Tong H; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Zhang L; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Patel M; Centre for Vascular Research, University of New South Wales, Kensington, Sydney, NSW 2052, Australia., Wang F; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Rames MJ; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Ren A; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Rye KA; Centre for Vascular Research, University of New South Wales, Kensington, Sydney, NSW 2052, Australia., Qiu X; Pfizer Inc., Groton, Connecticut 06340, USA., Johns DG; Merck Research Laboratories, Rahway, New Jersey 07065, USA., Charles MA; School of Medicine, University of California, San Francisco, California 94115, USA., Ren G; The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720. |
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Jazyk: | angličtina |
Zdroj: | Scientific reports [Sci Rep] 2015 Mar 04; Vol. 5, pp. 8741. Date of Electronic Publication: 2015 Mar 04. |
DOI: | 10.1038/srep08741 |
Abstrakt: | Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL. |
Databáze: | MEDLINE |
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