HDL biology
Electron microscopy shows CETP binds HDL through hydrophobic surface interactions, not protein contacts (Sci Rep 2015)
Original title: HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation
Although the crystal structure of cholesteryl ester transfer protein (CETP) was known, how it binds HDL to move cholesteryl esters to LDL remained unclear. Using electron microscopy and molecular dynamics simulations of various HDL-like particles, researchers found that CETP binds HDL through hydrophobic interactions rather than protein-protein contacts. The curvature of HDL surface lipids creates a hydrophobic environment that drives interaction with the hydrophobic distal end of CETP, independent of other HDL components such as apolipoproteins, cholesteryl esters, and triglycerides. The authors suggest disrupting these hydrophobic interactions could offer a new therapeutic strategy for blocking the CETP-HDL interaction.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.