5xjy
From Proteopedia
Cryo-EM structure of human ABCA1
Structural highlights
Disease[ABCA1_HUMAN] Tangier disease;Apolipoprotein A-I deficiency. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[ABCA1_HUMAN] cAMP-dependent and sulfonylurea-sensitive anion transporter. Key gatekeeper influencing intracellular cholesterol transport. Publication Abstract from PubMedABCA1, an ATP-binding cassette (ABC) subfamily A exporter, mediates the cellular efflux of phospholipids and cholesterol to the extracellular acceptor apolipoprotein A-I (apoA-I) for generation of nascent high-density lipoprotein (HDL). Mutations of human ABCA1 are associated with Tangier disease and familial HDL deficiency. Here, we report the cryo-EM structure of human ABCA1 with nominal resolutions of 4.1 A for the overall structure and 3.9 A for the massive extracellular domain. The nucleotide-binding domains (NBDs) display a nucleotide-free state, while the two transmembrane domains (TMDs) contact each other through a narrow interface in the intracellular leaflet of the membrane. In addition to TMDs and NBDs, two extracellular domains of ABCA1 enclose an elongated hydrophobic tunnel. Structural mapping of dozens of disease-related mutations allows potential interpretation of their diverse pathogenic mechanisms. Structural-based analysis suggests a plausible "lateral access" mechanism for ABCA1-mediated lipid export that may be distinct from the conventional alternating-access paradigm. Structure of the Human Lipid Exporter ABCA1.,Qian H, Zhao X, Cao P, Lei J, Yan N, Gong X Cell. 2017 Jun 15;169(7):1228-1239.e10. doi: 10.1016/j.cell.2017.05.020. Epub, 2017 Jun 8. PMID:28602350[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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