7R8C

The structure of human ABCG1

7R8C の概要

• エントリーDOI: 10.2210/pdb7r8c/pdb
• EMDBエントリー: 24315
• 分子名称: Isoform 4 of ATP-binding cassette sub-family G member 1 (1 entity in total)
• 機能のキーワード: sterol, lipids, abc transporter, lipid transport
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 148457.97

構造登録者

Sun, Y.,Li, X.,Long, T. (登録日: 2021-06-26, 公開日: 2021-09-08, 最終更新日: 2025-05-14)

主引用文献

Sun, Y.,Wang, J.,Long, T.,Qi, X.,Donnelly, L.,Elghobashi-Meinhardt, N.,Esparza, L.,Cohen, J.C.,Xie, X.S.,Hobbs, H.H.,Li, X.
Molecular basis of cholesterol efflux via ABCG subfamily transporters.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: The ABCG1 homodimer (G1) and ABCG5-ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter G family, are required for maintenance of cellular cholesterol levels. G5G8 mediates secretion of neutral sterols into bile and the gut lumen, whereas G1 transports cholesterol from macrophages to high-density lipoproteins (HDLs). The mechanisms used by G5G8 and G1 to recognize and export sterols remain unclear. Here, we report cryoelectron microscopy (cryo-EM) structures of human G5G8 in sterol-bound and human G1 in cholesterol- and ATP-bound states. Both transporters have a sterol-binding site that is accessible from the cytosolic leaflet. A second site is present midway through the transmembrane domains of G5G8. The Walker A motif of G8 adopts a unique conformation that accounts for the marked asymmetry in ATPase activities between the two nucleotide-binding sites of G5G8. These structures, along with functional validation studies, provide a mechanistic framework for understanding cholesterol efflux via ABC transporters.

PubMed: 34404721
DOI: 10.1073/pnas.2110483118

実験手法

ELECTRON MICROSCOPY (3.7 Å)