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-Structure paper
タイトル | Structural basis of transfer between lipoproteins by cholesteryl ester transfer protein. |
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ジャーナル・号・ページ | Nat Chem Biol, Vol. 8, Issue 4, Page 342-349, Year 2012 |
掲載日 | 2012年2月19日 |
著者 | Lei Zhang / Feng Yan / Shengli Zhang / Dongsheng Lei / M Arthur Charles / Giorgio Cavigiolio / Michael Oda / Ronald M Krauss / Karl H Weisgraber / Kerry-Anne Rye / Henry J Pownall / Xiayang Qiu / Gang Ren / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Chem Biol / PubMed:22344176 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 14.0 Å |
構造データ | EMDB-5346: EMDB-5347: |
由来 |
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