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| <StructureSection load='6wbl' size='340' side='right'caption='[[6wbl]], [[Resolution|resolution]] 5.13Å' scene=''> | | <StructureSection load='6wbl' size='340' side='right'caption='[[6wbl]], [[Resolution|resolution]] 5.13Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6wbl]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WBL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WBL FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6wbl]] is a 7 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=6WBL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WBL FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CBO:CARBENOXOLONE'>CBO</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 5.13Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PANX1, MRS1, UNQ2529/PRO6028 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CBO:CARBENOXOLONE'>CBO</scene></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wbl OCA], [http://pdbe.org/6wbl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wbl RCSB], [http://www.ebi.ac.uk/pdbsum/6wbl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wbl ProSAT]</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=6wbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wbl OCA], [https://pdbe.org/6wbl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wbl RCSB], [https://www.ebi.ac.uk/pdbsum/6wbl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wbl ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/PANX1_HUMAN PANX1_HUMAN]] Structural component of the gap junctions and the hemichannels. May play a role as a Ca(2+)-leak channel to regulate ER Ca(2+) homeostasis.<ref>PMID:16908669</ref> <ref>PMID:20829356</ref> | | [https://www.uniprot.org/uniprot/PANX1_HUMAN PANX1_HUMAN] Structural component of the gap junctions and the hemichannels. May play a role as a Ca(2+)-leak channel to regulate ER Ca(2+) homeostasis.<ref>PMID:16908669</ref> <ref>PMID:20829356</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Pannexin 1 (PANX1) is an ATP-permeable channel with critical roles in a variety of physiological functions such as blood pressure regulation(1), apoptotic cell clearance(2) and human oocyte development(3). Here we present several structures of human PANX1 in a heptameric assembly at resolutions of up to 2.8 angstrom, including an apo state, a caspase-7-cleaved state and a carbenoxolone-bound state. We reveal a gating mechanism that involves two ion-conducting pathways. Under normal cellular conditions, the intracellular entry of the wide main pore is physically plugged by the C-terminal tail. Small anions are conducted through narrow tunnels in the intracellular domain. These tunnels connect to the main pore and are gated by a long linker between the N-terminal helix and the first transmembrane helix. During apoptosis, the C-terminal tail is cleaved by caspase, allowing the release of ATP through the main pore. We identified a carbenoxolone-binding site embraced by W74 in the extracellular entrance and a role for carbenoxolone as a channel blocker. We identified a gap-junction-like structure using a glycosylation-deficient mutant, N255A. Our studies provide a solid foundation for understanding the molecular mechanisms underlying the channel gating and inhibition of PANX1 and related large-pore channels.
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| Structures of human pannexin 1 reveal ion pathways and mechanism of gating.,Ruan Z, Orozco IJ, Du J, Lu W Nature. 2020 Jun 3. pii: 10.1038/s41586-020-2357-y. doi:, 10.1038/s41586-020-2357-y. PMID:32494015<ref>PMID:32494015</ref>
| | ==See Also== |
| | | *[[Pannexin|Pannexin]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6wbl" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Du, J]] | | [[Category: Du J]] |
| [[Category: Lu, W]] | | [[Category: Lu W]] |
| [[Category: Ruan, Z]] | | [[Category: Ruan Z]] |
| [[Category: Ion channel]]
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| [[Category: Transport protein]]
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