| Autor: |
Zhang L; Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California, USA., Yan F, Zhang S, Lei D, Charles MA, Cavigiolio G, Oda M, Krauss RM, Weisgraber KH, Rye KA, Pownall HJ, Qiu X, Ren G |
| Jazyk: |
angličtina |
| Zdroj: |
Nature chemical biology [Nat Chem Biol] 2012 Feb 19; Vol. 8 (4), pp. 342-9. Date of Electronic Publication: 2012 Feb 19. |
| DOI: |
10.1038/nchembio.796 |
| Abstrakt: |
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 β-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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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