|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='6wbk' size='340' side='right'caption='[[6wbk]], [[Resolution|resolution]] 6.01Å' scene=''> | | <StructureSection load='6wbk' size='340' side='right'caption='[[6wbk]], [[Resolution|resolution]] 6.01Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wbk]] 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=6WBK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WBK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wbk]] 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=6WBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WBK FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.01Å</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=6wbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wbk OCA], [http://pdbe.org/6wbk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wbk RCSB], [http://www.ebi.ac.uk/pdbsum/6wbk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wbk 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=6wbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wbk OCA], [https://pdbe.org/6wbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wbk RCSB], [https://www.ebi.ac.uk/pdbsum/6wbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wbk 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;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | 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.
| + | |
| | | | |
| - | 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>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6wbk" style="background-color:#fffaf0;"></div>
| + | |
| | == 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]]
| + | |
| - | [[Category: Transport protein]]
| + | |
