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TitleStructure of the Human Cholesterol Transporter ABCG1.
Journal, issue, pagesJ Mol Biol, Vol. 433, Issue 21, Page 167218, Year 2021
Publish dateOct 15, 2021
AuthorsLiga Skarda / Julia Kowal / Kaspar P Locher /
PubMed AbstractABCG1 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 linksJ Mol Biol / PubMed:34461069
MethodsEM (single particle)
Resolution4.0 Å
Structure data

EMDB-13118, PDB-7oz1:
Cryo-EM structure of ABCG1 E242Q mutant with ATP and cholesteryl hemisuccinate bound
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-PEE:
1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipid*YM / Discrete optimized protein energy

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / cholesterol / ABC transporter / ATP binding / inward-open

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