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Structural basis of transfer between lipoproteins by cholesteryl ester transfer protein.
- Source :
-
Nature Chemical Biology . Apr2012, Vol. 8 Issue 4, p342-349. 8p. 1 Color Photograph, 3 Black and White Photographs, 2 Diagrams, 1 Graph. - Publication Year :
- 2012
-
Abstract
- 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 ?-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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15524450
- Volume :
- 8
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Nature Chemical Biology
- Publication Type :
- Academic Journal
- Accession number :
- 73444295
- Full Text :
- https://doi.org/10.1038/nchembio.796