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-Structure paper
Title | Structure of the Human Cholesterol Transporter ABCG1. |
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Journal, issue, pages | J Mol Biol, Vol. 433, Issue 21, Page 167218, Year 2021 |
Publish date | Oct 15, 2021 |
Authors | Liga Skarda / Julia Kowal / Kaspar P Locher / |
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 ...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. |
External links | J Mol Biol / PubMed:34461069 |
Methods | EM (single particle) |
Resolution | 4.0 Å |
Structure data | EMDB-13118, PDB-7oz1: |
Chemicals | ChemComp-ATP: ChemComp-Y01: ChemComp-PEE: |
Source |
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Keywords | MEMBRANE PROTEIN / cholesterol / ABC transporter / ATP binding / inward-open |