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TitleStructure and transport mechanism of the human cholesterol transporter ABCG1.
Journal, issue, pagesCell Rep, Vol. 38, Issue 4, Page 110298, Year 2022
Publish dateJan 25, 2022
AuthorsDa Xu / Yanyan Li / Fengrui Yang / Cai-Rong Sun / Jinheng Pan / Liang Wang / Zhi-Peng Chen / Shu-Cheng Fang / Xuebiao Yao / Wen-Tao Hou / Cong-Zhao Zhou / Yuxing Chen /
PubMed AbstractThe reverse cholesterol transport pathway is responsible for the maintenance of human cholesterol homeostasis, an imbalance of which usually leads to atherosclerosis. As a key component of this ...The reverse cholesterol transport pathway is responsible for the maintenance of human cholesterol homeostasis, an imbalance of which usually leads to atherosclerosis. As a key component of this pathway, the ATP-binding cassette transporter ABCG1 forwards cellular cholesterol to the extracellular acceptor nascent high-density lipoprotein (HDL). Here, we report a 3.26-Å cryo-electron microscopy structure of cholesterol-bound ABCG1 in an inward-facing conformation, which represents a turnover condition upon ATP binding. Structural analyses combined with functional assays reveals that a cluster of conserved hydrophobic residues, in addition to two sphingomyelins, constitute a well-defined cholesterol-binding cavity. The exit of this cavity is closed by three pairs of conserved Phe residues, which constitute a hydrophobic path for the release of cholesterol in an acceptor concentration-dependent manner. Overall, we propose an ABCG1-driven cholesterol transport cycle initiated by sphingomyelin-assisted cholesterol recruitment and accomplished by the release of cholesterol to HDL.
External linksCell Rep / PubMed:35081353
MethodsEM (single particle)
Resolution3.26 Å
Structure data

EMDB-31547, PDB-7fdv:
Cryo-EM structure of the human cholesterol transporter ABCG1 in complex with cholesterol
Method: EM (single particle) / Resolution: 3.26 Å

Chemicals

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

ChemComp-HWP:
[(E,2S,3R)-2-(hexadecanoylamino)-3-oxidanyl-octadec-4-enyl] 2-(trimethylazaniumyl)ethyl phosphate

ChemComp-CLR:
CHOLESTEROL

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Human ABCG1 / cholsterol transporter / ATP-bound / cholesterol

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