6nt4
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
==Cryo-EM structure of a human-cockroach hybrid Nav channel bound to alpha-scorpion toxin AaH2.== | ==Cryo-EM structure of a human-cockroach hybrid Nav channel bound to alpha-scorpion toxin AaH2.== | ||
| - | <StructureSection load='6nt4' size='340' side='right' caption='[[6nt4]], [[Resolution|resolution]] 3.50Å' scene=''> | + | <StructureSection load='6nt4' size='340' side='right'caption='[[6nt4]], [[Resolution|resolution]] 3.50Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6nt4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Androctonus_australis Androctonus australis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NT4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NT4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nt4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/American_cockroach American cockroach] and [http://en.wikipedia.org/wiki/Androctonus_australis Androctonus australis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NT4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NT4 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=L0A:Digitonin'>L0A</scene>, <scene name='pdbligand=LHG:1,2-DIPALMITOYL-PHOSPHATIDYL-GLYCEROLE'>LHG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=L0A:Digitonin'>L0A</scene>, <scene name='pdbligand=LHG:1,2-DIPALMITOYL-PHOSPHATIDYL-GLYCEROLE'>LHG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6nt3|6nt3]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6nt3|6nt3]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SCN9A, NENA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6978 American cockroach])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nt4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nt4 OCA], [http://pdbe.org/6nt4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nt4 RCSB], [http://www.ebi.ac.uk/pdbsum/6nt4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nt4 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nt4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nt4 OCA], [http://pdbe.org/6nt4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nt4 RCSB], [http://www.ebi.ac.uk/pdbsum/6nt4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nt4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/SCNA1_PERAM SCNA1_PERAM]] Mediates the voltage-dependent sodium ion permeability of excitable membranes.[RuleBase:RU361132]<ref>PMID:28183995</ref> [[http://www.uniprot.org/uniprot/SCX2_ANDAU SCX2_ANDAU]] Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals. | [[http://www.uniprot.org/uniprot/SCNA1_PERAM SCNA1_PERAM]] Mediates the voltage-dependent sodium ion permeability of excitable membranes.[RuleBase:RU361132]<ref>PMID:28183995</ref> [[http://www.uniprot.org/uniprot/SCX2_ANDAU SCX2_ANDAU]] Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fast inactivation of voltage-gated sodium (Nav) channels is essential for electrical signaling, but its mechanism remains poorly understood. Here we determined the structures of a eukaryotic Nav channel alone and in complex with a lethal alpha-scorpion toxin, AaH2, by electron microscopy, both at 3.5-angstrom resolution. AaH2 wedges into voltage-sensing domain IV (VSD4) to impede fast activation by trapping a deactivated state in which gating charge interactions bridge to the acidic intracellular carboxyl-terminal domain. In the absence of AaH2, the S4 helix of VSD4 undergoes a ~13-angstrom translation to unlatch the intracellular fast-inactivation gating machinery. Highlighting the polypharmacology of alpha-scorpion toxins, AaH2 also targets an unanticipated receptor site on VSD1 and a pore glycan adjacent to VSD4. Overall, this work provides key insights into fast inactivation, electromechanical coupling, and pathogenic mutations in Nav channels. | ||
| + | |||
| + | Structural basis of alpha-scorpion toxin action on Nav channels.,Clairfeuille T, Cloake A, Infield DT, Llongueras JP, Arthur CP, Li ZR, Jian Y, Martin-Eauclaire MF, Bougis PE, Ciferri C, Ahern CA, Bosmans F, Hackos DH, Rohou A, Payandeh J Science. 2019 Mar 22;363(6433). pii: science.aav8573. doi:, 10.1126/science.aav8573. Epub 2019 Feb 7. PMID:30733386<ref>PMID:30733386</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6nt4" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: American cockroach]] | ||
[[Category: Androctonus australis]] | [[Category: Androctonus australis]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Clairfeuille, T]] | [[Category: Clairfeuille, T]] | ||
[[Category: Payandeh, J]] | [[Category: Payandeh, J]] | ||
Revision as of 11:44, 18 December 2019
Cryo-EM structure of a human-cockroach hybrid Nav channel bound to alpha-scorpion toxin AaH2.
| |||||||||||
