7OZ1

Cryo-EM structure of ABCG1 E242Q mutant with ATP and cholesteryl hemisuccinate bound

Summary for 7OZ1

• Entry DOI: 10.2210/pdb7oz1/pdb
• EMDB information: 13118
• Descriptor: Isoform 4 of ATP-binding cassette sub-family G member 1, ADENOSINE-5'-TRIPHOSPHATE, CHOLESTEROL HEMISUCCINATE, ... (4 entities in total)
• Functional Keywords: cholesterol, abc transporter, atp binding, inward-open, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 157713.25

Authors

Skarda, L.,Kowal, J.,Locher, K.P. (deposition date: 2021-06-25, release date: 2021-09-22, Last modification date: 2021-09-29)

Primary citation

Skarda, L.,Kowal, J.,Locher, K.P.
Structure of the Human Cholesterol Transporter ABCG1.
J.Mol.Biol., 433:167218-167218, 2021

PubMed Abstract: ABCG1 is an ATP binding cassette (ABC) transporter that removes excess cholesterol from peripheral tissues. Despite its role in preventing lipid accumulation and the development of cardiovascular and metabolic disease, the mechanism underpinning ABCG1-mediated cholesterol transport is unknown. Here we report a cryo-EM structure of human ABCG1 at 4 Å resolution in an inward-open state, featuring sterol-like density in the binding cavity. Structural comparison with the multidrug transporter ABCG2 and the sterol transporter ABCG5/G8 reveals the basis of mechanistic differences and distinct substrate specificity. Benzamil and taurocholate inhibited the ATPase activity of liposome-reconstituted ABCG1, whereas the ABCG2 inhibitor Ko143 did not. Based on the structural insights into ABCG1, we propose a mechanism for ABCG1-mediated cholesterol transport.

PubMed: 34461069
DOI: 10.1016/j.jmb.2021.167218

Experimental method

ELECTRON MICROSCOPY (4 Å)