8CUB

Crystal Structure of ABCG5/G8 in Complex with Cholesterol

8CUB の概要

• エントリーDOI: 10.2210/pdb8cub/pdb
• 分子名称: ATP-binding cassette sub-family G member 5, ATP-binding cassette sub-family G member 8, CHOLESTEROL (3 entities in total)
• 機能のキーワード: abcg5, abcg8, membrane protein, cholesterol transporter, translocase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 303763.92

構造登録者

Rezaei, F.,Farhat, D.,Lee, J.Y. (登録日: 2022-05-17, 公開日: 2022-08-31, 最終更新日: 2023-10-18)

主引用文献

Farhat, D.,Rezaei, F.,Ristovski, M.,Yang, Y.,Stancescu, A.,Dzimkova, L.,Samnani, S.,Couture, J.F.,Lee, J.Y.
Structural Analysis of Cholesterol Binding and Sterol Selectivity by ABCG5/G8.
J.Mol.Biol., 434:167795-167795, 2022

PubMed Abstract: The ATP-binding cassette (ABC) sterol transporters are responsible for maintaining cholesterol homeostasis in mammals by participating in reverse cholesterol transport (RCT) or transintestinal cholesterol efflux (TICE). The heterodimeric ABCG5/G8 carries out selective sterol excretion, preventing the abnormal accumulation of plant sterols in human bodies, while homodimeric ABCG1 contributes to the biogenesis and metabolism of high-density lipoproteins. A sterol-binding site on ABCG5/G8 was proposed at the interface of the transmembrane domain and the core of lipid bilayers. In this study, we have determined the crystal structure of ABCG5/G8 in a cholesterol-bound state. The structure combined with amino acid sequence analysis shows that in the proximity of the sterol-binding site, a highly conserved phenylalanine array supports functional implications for ABCG cholesterol/sterol transporters. Lastly, in silico docking analysis of cholesterol and stigmasterol (a plant sterol) suggests sterol-binding selectivity on ABCG5/G8, but not ABCG1. Together, our results provide a structural basis for cholesterol binding on ABCG5/G8 and the sterol selectivity by ABCG transporters.

PubMed: 35988751
DOI: 10.1016/j.jmb.2022.167795

実験手法

X-RAY DIFFRACTION (4.05 Å)