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7tc0
From Proteopedia
(Difference between revisions)
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==The structure of human ABCA1 in digitonin== | ==The structure of human ABCA1 in digitonin== | ||
| - | <StructureSection load='7tc0' size='340' side='right'caption='[[7tc0]]' scene=''> | + | <StructureSection load='7tc0' size='340' side='right'caption='[[7tc0]], [[Resolution|resolution]] 3.10Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TC0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7tc0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TC0 FirstGlance]. <br> |
| - | </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=7tc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tc0 OCA], [https://pdbe.org/7tc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tc0 RCSB], [https://www.ebi.ac.uk/pdbsum/7tc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tc0 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7tc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tc0 OCA], [https://pdbe.org/7tc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tc0 RCSB], [https://www.ebi.ac.uk/pdbsum/7tc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tc0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/ABCA1_HUMAN 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 == | ||
| + | [https://www.uniprot.org/uniprot/ABCA1_HUMAN ABCA1_HUMAN] cAMP-dependent and sulfonylurea-sensitive anion transporter. Key gatekeeper influencing intracellular cholesterol transport. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | ATP-binding cassette transporter A1 (ABCA1) utilizes energy derived from ATP hydrolysis to export cholesterol and phospholipids from macrophages. ABCA1 plays a central role in the biosynthesis of high-density lipoprotein (HDL), which mediates reverse cholesterol transport and prevents detrimental lipid deposition. Mutations in ABCA1 cause Tangier disease characterized by a remarkable reduction in the amount of HDL in blood. Here we present cryo-electron microscopy structures of human ABCA1 in ATP-bound and nucleotide-free states. Structural comparison reveals that ATP molecules pull the nucleotide-binding domains together, inducing movements of transmembrane helices 1, 2, 7 and 8 through a series of salt-bridge interactions. Subsequently, extracellular domains (ECDs) undergo a rotation and introduce conformational changes in the ECD-transmembrane interface. In addition, while we observe a sterol-like molecule in ECDs, no such density was observed in the structure of an HDL-deficiency mutant ABCA1(Y482C), demonstrating the physiological importance of ECDs and a putative interaction mode between ABCA1 and its lipid acceptors. Thus, these structures, along with cholesterol efflux assays, advance the understanding ABCA1-mediated reverse cholesterol transport. | ||
| + | |||
| + | Cholesterol efflux mechanism revealed by structural analysis of human ABCA1 conformational states.,Sun Y, Li X Nat Cardiovasc Res. 2022;1(3):238-245. doi: 10.1038/s44161-022-00022-y. Epub 2022 , Mar 3. PMID:37181814<ref>PMID:37181814</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7tc0" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[ABC transporter 3D structures|ABC transporter 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Li X]] | [[Category: Li X]] | ||
[[Category: Sun Y]] | [[Category: Sun Y]] | ||
Current revision
The structure of human ABCA1 in digitonin
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