7fdv
From Proteopedia
Cryo-EM structure of the human cholesterol transporter ABCG1 in complex with cholesterol
Structural highlights
FunctionABCG1_HUMAN Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta-hydroxycholesterol and this transport is coupled to hydrolysis of ATP (PubMed:17408620, PubMed:24576892). The lipid efflux is ALB-dependent (PubMed:16702602). Is an active component of the macrophage lipid export complex. Could also be involved in intracellular lipid transport processes. The role in cellular lipid homeostasis may not be limited to macrophages. Prevents cell death by transporting cytotoxic 7beta-hydroxycholesterol (PubMed:17408620).[1] [2] [3] Publication Abstract from PubMedThe 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-A 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. Structure and transport mechanism of the human cholesterol transporter ABCG1.,Xu D, Li Y, Yang F, Sun CR, Pan J, Wang L, Chen ZP, Fang SC, Yao X, Hou WT, Zhou CZ, Chen Y Cell Rep. 2022 Jan 25;38(4):110298. doi: 10.1016/j.celrep.2022.110298. PMID:35081353[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Chen Y | Chen ZP | Fang SC | Hou WT | Li YY | Pan JH | Sun CR | Wang L | Xu D | Yang FR | Yao XB | Zhou CZ
