7FDV

Cryo-EM structure of the human cholesterol transporter ABCG1 in complex with cholesterol

Summary for 7FDV

• Entry DOI: 10.2210/pdb7fdv/pdb
• EMDB information: 31547
• Descriptor: ATP-binding cassette sub-family G member 1, ADENOSINE-5'-TRIPHOSPHATE, [(E,2S,3R)-2-(hexadecanoylamino)-3-oxidanyl-octadec-4-enyl] 2-(trimethylazaniumyl)ethyl phosphate, ... (4 entities in total)
• Functional Keywords: human abcg1, cholsterol transporter, atp-bound, cholesterol, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 154535.41

Authors

Xu, D.,Li, Y.Y.,Yang, F.R.,Sun, C.R.,Pan, J.H.,Wang, L.,Chen, Z.P.,Fang, S.C.,Yao, X.B.,Hou, W.T.,Zhou, C.Z.,Chen, Y. (deposition date: 2021-07-18, release date: 2022-06-22, Last modification date: 2024-06-12)

Primary citation

Xu, D.,Li, Y.,Yang, F.,Sun, C.R.,Pan, J.,Wang, L.,Chen, Z.P.,Fang, S.C.,Yao, X.,Hou, W.T.,Zhou, C.Z.,Chen, Y.
Structure and transport mechanism of the human cholesterol transporter ABCG1.
Cell Rep, 38:110298-110298, 2022

PubMed Abstract: 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.

PubMed: 35081353
DOI: 10.1016/j.celrep.2022.110298

Experimental method

ELECTRON MICROSCOPY (3.26 Å)