EMD-13118
Cryo-EM structure of ABCG1 E242Q mutant with ATP and cholesteryl hemisuccinate bound
EMD-13118
Single-particle4.0 Å
Deposition: 25/06/2021Map released: 22/09/2021
Last modified: 29/09/2021
Sample Organism:
Homo sapiens
Sample: Human ABCG1 with bound ATP and CHS
Fitted models: 7oz1 (Avg. Q-score: 0.466)
Deposition Authors: Skarda L, Kowal J, Locher KP
Sample: Human ABCG1 with bound ATP and CHS
Fitted models: 7oz1 (Avg. Q-score: 0.466)
Deposition Authors: Skarda L, Kowal J, Locher KP
Structure of the Human Cholesterol Transporter ABCG1.
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.
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.