| Structural highlights
Function
ABCG1_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 PubMed
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-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
- ↑ Kobayashi A, Takanezawa Y, Hirata T, Shimizu Y, Misasa K, Kioka N, Arai H, Ueda K, Matsuo M. Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1. J Lipid Res. 2006 Aug;47(8):1791-802. doi: 10.1194/jlr.M500546-JLR200. Epub 2006 , May 15. PMID:16702602 doi:http://dx.doi.org/10.1194/jlr.M500546-JLR200
- ↑ Engel T, Kannenberg F, Fobker M, Nofer JR, Bode G, Lueken A, Assmann G, Seedorf U. Expression of ATP binding cassette-transporter ABCG1 prevents cell death by transporting cytotoxic 7beta-hydroxycholesterol. FEBS Lett. 2007 Apr 17;581(8):1673-80. doi: 10.1016/j.febslet.2007.03.038. Epub, 2007 Mar 28. PMID:17408620 doi:http://dx.doi.org/10.1016/j.febslet.2007.03.038
- ↑ Gu HM, Wang FQ, Zhang DW. Caveolin-1 interacts with ATP binding cassette transporter G1 (ABCG1) and regulates ABCG1-mediated cholesterol efflux. Biochim Biophys Acta. 2014 Jun;1841(6):847-58. doi: 10.1016/j.bbalip.2014.02.002., Epub 2014 Feb 24. PMID:24576892 doi:http://dx.doi.org/10.1016/j.bbalip.2014.02.002
- ↑ Xu D, Li Y, Yang F, Sun CR, Pan J, Wang L, Chen ZP, Fang SC, Yao X, Hou WT, Zhou CZ, Chen Y. Structure and transport mechanism of the human cholesterol transporter ABCG1. Cell Rep. 2022 Jan 25;38(4):110298. doi: 10.1016/j.celrep.2022.110298. PMID:35081353 doi:http://dx.doi.org/10.1016/j.celrep.2022.110298
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