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HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation.

ABSTRACT: 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.

SUBMITTER: Zhang M

PROVIDER: S-EPMC4348656 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation.

Zhang Meng M Charles River R Tong Huimin H Zhang Lei L Patel Mili M Wang Francis F Rames Matthew J MJ Ren Amy A Rye Kerry-Anne KA Qiu Xiayang X Johns Douglas G DG Charles M Arthur MA Ren Gang G

Scientific reports 20150304

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 inte ...[more]

PMID: 25737239

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Dataset Information

HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation.

Publications

HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation.

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