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

• DOI: 10.1038/srep08741
• Publication Date: 2015-03-04T10:06:42Z
• Authors: Meng Zhang; River Charles; Huimin Tong; Lei Zhang; Mili Patel; Francis Wang; Matthew J. Rames; Amy Ren; Kerry-Anne Rye; Xiayang Qiu; Douglas G. Johns; M. Arthur Charles; Gang Ren
• Keywords: Dynamics

Abstract Cholesteryl ester transfer protein (CETP) mediates the of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing risk cardiovascular diseases (CVD). Although crystal structure is known, little known regarding how binds HDL. Here, we investigated various HDL-like particles interact with by electron microscopy molecular dynamics simulations. Results showed that via hydrophobic interactions rather than protein-protein interactions. The surface lipid curvature generates environment, leading distal end interaction. This interaction independent other components, such apolipoproteins, cholesteryl triglycerides. Thus, disrupting these could be new therapeutic attenuating