7R8B

The structure of human ABCG5/ABCG8 supplemented with cholesterol

Summary for 7R8B

• Entry DOI: 10.2210/pdb7r8b/pdb
• EMDB information: 24314
• Descriptor: ATP-binding cassette sub-family G member 5, ATP-binding cassette sub-family G member 8, 2C7 Fab heavy chain, ... (5 entities in total)
• Functional Keywords: sterol, lipids, abc transporter, lipid transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 207561.80

Authors

Sun, Y.,Li, X.,Long, T. (deposition date: 2021-06-26, release date: 2021-09-08, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.1 Å)