Paper Citing NAMD - Abstract
Zhang, Lei; Yan, Feng; Zhang, Shengli; Lei, Dongsheng; Charles, M. Arthur; Cavigiolio, Giorgio; Oda, Michael; Krauss, Ronald M.; Weisgraber, Karl H.; Rye, Kerry-Anne; Pownall, Henry J.; Qiu, Xiayang; Ren, Gang
Structural basis of transfer between lipoproteins by cholesteryl ester transfer protein
NATURE CHEMICAL BIOLOGY, 8:342-349, APR 2012
Human cholesteryl ester transfer protein (CETP) mediates the net transfer of cholesteryl ester mass from atheroprotective high-density lipoproteins to atherogenic low-density lipoproteins by an unknown mechanism. Delineating this mechanism would be an important step toward the rational design of new CETP inhibitors for treating cardiovascular diseases. Using EM, single-particle image processing and molecular dynamics simulation, we discovered that CETP bridges a ternary complex with its N-terminal beta-barrel domain penetrating into high-density lipoproteins and its C-terminal domain interacting with low-density lipoprotein or very-low-density lipoprotein. In our mechanistic model, the CETP lipoprotein-interacting regions, which are highly mobile, form pores that connect to a hydrophobic central cavity, thereby forming a tunnel for transfer of neutral lipids from donor to acceptor lipoproteins. These new insights into CETP transfer provide a molecular basis for analyzing mechanisms for CETP inhibition.
