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| | <StructureSection load='6wbf' size='340' side='right'caption='[[6wbf]], [[Resolution|resolution]] 2.83Å' scene=''> | | <StructureSection load='6wbf' size='340' side='right'caption='[[6wbf]], [[Resolution|resolution]] 2.83Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wbf]] 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=6WBF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WBF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wbf]] is a 7 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=6WBF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WBF FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=DGA:DIACYL+GLYCEROL'>DGA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEH:DI-STEAROYL-3-SN-PHOSPHATIDYLETHANOLAMINE'>PEH</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=DGA:DIACYL+GLYCEROL'>DGA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEH:DI-STEAROYL-3-SN-PHOSPHATIDYLETHANOLAMINE'>PEH</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PANX1, MRS1, UNQ2529/PRO6028 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6wbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wbf OCA], [http://pdbe.org/6wbf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wbf RCSB], [http://www.ebi.ac.uk/pdbsum/6wbf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wbf 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=6wbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wbf OCA], [https://pdbe.org/6wbf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wbf RCSB], [https://www.ebi.ac.uk/pdbsum/6wbf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wbf 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Structural highlights
6wbf is a 7 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , |
| Gene: | PANX1, MRS1, UNQ2529/PRO6028 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[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.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vanden Abeele F, Bidaux G, Gordienko D, Beck B, Panchin YV, Baranova AV, Ivanov DV, Skryma R, Prevarskaya N. Functional implications of calcium permeability of the channel formed by pannexin 1. J Cell Biol. 2006 Aug 14;174(4):535-46. doi: 10.1083/jcb.200601115. PMID:16908669 doi:http://dx.doi.org/10.1083/jcb.200601115
- ↑ Bunse S, Schmidt M, Prochnow N, Zoidl G, Dermietzel R. Intracellular cysteine 346 is essentially involved in regulating Panx1 channel activity. J Biol Chem. 2010 Dec 3;285(49):38444-52. doi: 10.1074/jbc.M110.101014. Epub 2010, Sep 9. PMID:20829356 doi:http://dx.doi.org/10.1074/jbc.M110.101014
- ↑ Ruan Z, Orozco IJ, Du J, Lu W. Structures of human pannexin 1 reveal ion pathways and mechanism of gating. Nature. 2020 Jun 3. pii: 10.1038/s41586-020-2357-y. doi:, 10.1038/s41586-020-2357-y. PMID:32494015 doi:http://dx.doi.org/10.1038/s41586-020-2357-y
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