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6wbg

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Revision as of 15:21, 8 June 2021

Cryo-EM structure of human Pannexin 1 channel with its C-terminal tail cleaved by caspase-7

Structural highlights

6wbg 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6wbg"

@@ Line 3: / Line 3: @@
 <StructureSection load='6wbg' size='340' side='right'caption='[[6wbg]], [[Resolution|resolution]] 2.97&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6wbg]] 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=6WBG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WBG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6wbg]] 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=6WBG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WBG 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>
-<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=6wbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wbg OCA], [http://pdbe.org/6wbg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wbg RCSB], [http://www.ebi.ac.uk/pdbsum/6wbg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wbg 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=6wbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wbg OCA], [https://pdbe.org/6wbg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wbg RCSB], [https://www.ebi.ac.uk/pdbsum/6wbg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wbg ProSAT]</span></td></tr>
 </table>
 == 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 ==

6wbg

From Proteopedia

Revision as of 15:21, 8 June 2021

Cryo-EM structure of human Pannexin 1 channel with its C-terminal tail cleaved by caspase-7

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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