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7e7i
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Cryo-EM structure of human ABCA4 in the apo state== |
| + | <StructureSection load='7e7i' size='340' side='right'caption='[[7e7i]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7e7i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E7I FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ABCA4, ABCR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/P-type_phospholipid_transporter P-type phospholipid transporter], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=7.6.2.1 7.6.2.1] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7e7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e7i OCA], [https://pdbe.org/7e7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e7i RCSB], [https://www.ebi.ac.uk/pdbsum/7e7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e7i ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[https://www.uniprot.org/uniprot/ABCA4_HUMAN ABCA4_HUMAN]] Cone rod dystrophy;NON RARE IN EUROPE: Age-related macular degeneration;Stargardt disease;Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/ABCA4_HUMAN ABCA4_HUMAN]] Catalyzes the translocation of specific phospholipids from the extracellular/lumenal to the cytoplasmic leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylethanolamine (PubMed:24097981). In the visual cycle, acts as an inward-directed retinoid flipase, retinoid substrates imported by ABCA4 from the extracellular or intradiscal (rod) membrane surfaces to the cytoplasmic membrane surface are all-trans-retinaldehyde (ATR) and N-retinyl-phosphatidyl-ethanolamine (NR-PE). Once transported to the cytoplasmic surface, ATR is reduced to vitamin A by trans-retinol dehydrogenase (tRDH) and then transferred to the retinal pigment epithelium (RPE) where it is converted to 11-cis-retinal. May play a role in photoresponse, removing ATR/NR-PE from the extracellular photoreceptor surfaces during bleach recovery.<ref>PMID:10075733</ref> <ref>PMID:24097981</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human ATP-binding cassette (ABC) subfamily A (ABCA) transporters mediate the transport of various lipid compounds across the membrane. Mutations in human ABCA transporters have been described to cause severe hereditary disorders associated with impaired lipid transport. However, little is known about the mechanistic details of substrate recognition and translocation by ABCA transporters. Here, we present three cryo-EM structures of human ABCA4, a retina-specific ABCA transporter, in distinct functional states at resolutions of 3.3-3.4 A. In the nucleotide-free state, the two transmembrane domains (TMDs) exhibit a lateral-opening conformation, allowing the lateral entry of substrate from the lipid bilayer. The N-retinylidene-phosphatidylethanolamine (NRPE), the physiological lipid substrate of ABCA4, is sandwiched between the two TMDs in the luminal leaflet and is further stabilized by an extended loop from extracellular domain 1. In the ATP-bound state, the two TMDs display a closed conformation, which precludes the substrate binding. Our study provides a molecular basis to understand the mechanism of ABCA4-mediated NRPE recognition and translocation, and suggests a common 'lateral access and extrusion' mechanism for ABCA-mediated lipid transport. | ||
| - | + | Structural basis of substrate recognition and translocation by human ABCA4.,Xie T, Zhang Z, Fang Q, Du B, Gong X Nat Commun. 2021 Jun 22;12(1):3853. doi: 10.1038/s41467-021-24194-6. PMID:34158497<ref>PMID:34158497</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7e7i" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: P-type phospholipid transporter]] | ||
| + | [[Category: Gong, X]] | ||
| + | [[Category: Xie, T]] | ||
| + | [[Category: Zhang, Z K]] | ||
| + | [[Category: Lipid transport]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Translocase]] | ||
Current revision
Cryo-EM structure of human ABCA4 in the apo state
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