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-Structure paper
タイトル | Structure and transport mechanism of the human cholesterol transporter ABCG1. |
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ジャーナル・号・ページ | Cell Rep, Vol. 38, Issue 4, Page 110298, Year 2022 |
掲載日 | 2022年1月25日 |
著者 | Da Xu / Yanyan Li / Fengrui Yang / Cai-Rong Sun / Jinheng Pan / Liang Wang / Zhi-Peng Chen / Shu-Cheng Fang / Xuebiao Yao / Wen-Tao Hou / Cong-Zhao Zhou / Yuxing Chen / |
PubMed 要旨 | The reverse cholesterol transport pathway is responsible for the maintenance of human cholesterol homeostasis, an imbalance of which usually leads to atherosclerosis. As a key component of this ...The reverse cholesterol transport pathway is responsible for the maintenance of human cholesterol homeostasis, an imbalance of which usually leads to atherosclerosis. As a key component of this pathway, the ATP-binding cassette transporter ABCG1 forwards cellular cholesterol to the extracellular acceptor nascent high-density lipoprotein (HDL). Here, we report a 3.26-Å cryo-electron microscopy structure of cholesterol-bound ABCG1 in an inward-facing conformation, which represents a turnover condition upon ATP binding. Structural analyses combined with functional assays reveals that a cluster of conserved hydrophobic residues, in addition to two sphingomyelins, constitute a well-defined cholesterol-binding cavity. The exit of this cavity is closed by three pairs of conserved Phe residues, which constitute a hydrophobic path for the release of cholesterol in an acceptor concentration-dependent manner. Overall, we propose an ABCG1-driven cholesterol transport cycle initiated by sphingomyelin-assisted cholesterol recruitment and accomplished by the release of cholesterol to HDL. |
リンク | Cell Rep / PubMed:35081353 |
手法 | EM (単粒子) |
解像度 | 3.26 Å |
構造データ | EMDB-31547, PDB-7fdv: |
化合物 | ChemComp-ATP: ChemComp-HWP: ChemComp-CLR: |
由来 |
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キーワード | MEMBRANE PROTEIN / Human ABCG1 / cholsterol transporter / ATP-bound / cholesterol |