7oz1

From Proteopedia

Jump to: navigation, search

Cryo-EM structure of ABCG1 E242Q mutant with ATP and cholesteryl hemisuccinate bound

Structural highlights

7oz1 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:ATP, PEE, Y01
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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 A 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.

Structure of the Human Cholesterol Transporter ABCG1.,Skarda L, Kowal J, Locher KP J Mol Biol. 2021 Aug 28;433(21):167218. doi: 10.1016/j.jmb.2021.167218. PMID:34461069[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
6 reviews cite this structure
Snapshots of ABCG1 and ABCG5/G8: A Sterol's Journey to Cross the Cellular Membranes.
Rezaei et al. (2022)
5 more
8 other articles
No citations found

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ Skarda L, Kowal J, Locher KP. Structure of the Human Cholesterol Transporter ABCG1. J Mol Biol. 2021 Aug 28;433(21):167218. doi: 10.1016/j.jmb.2021.167218. PMID:34461069 doi:http://dx.doi.org/10.1016/j.jmb.2021.167218

Contents


PDB ID 7oz1

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/7oz1"
Personal tools