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6nt4

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Revision as of 03:32, 11 April 2020

Cryo-EM structure of a human-cockroach hybrid Nav channel bound to alpha-scorpion toxin AaH2.

6nt4, resolution 3.50Å

Structural highlights

6nt4 is a 3 chain structure with sequence from American cockroach and Androctonus australis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	6nt3
Gene:	SCN9A, NENA (American cockroach)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SCNA1_PERAM] Mediates the voltage-dependent sodium ion permeability of excitable membranes.[RuleBase:RU361132]^[1] [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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shen H, Zhou Q, Pan X, Li Z, Wu J, Yan N. Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution. Science. 2017 Mar 3;355(6328). pii: eaal4326. doi: 10.1126/science.aal4326. Epub , 2017 Feb 9. PMID:28183995 doi:http://dx.doi.org/10.1126/science.aal4326
↑ 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. Structural basis of alpha-scorpion toxin action on Nav channels. Science. 2019 Mar 22;363(6433). pii: science.aav8573. doi:, 10.1126/science.aav8573. Epub 2019 Feb 7. PMID:30733386 doi:http://dx.doi.org/10.1126/science.aav8573

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/6nt4"

@@ Line 3: / Line 3: @@
 <SX load='6nt4' size='340' side='right' viewer='molstar' caption='[[6nt4]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<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://proteopedia.org/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" id="ligandDat"><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='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://proteopedia.org/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>
 == Function ==

6nt4

From Proteopedia

Revision as of 03:32, 11 April 2020

Cryo-EM structure of a human-cockroach hybrid Nav channel bound to alpha-scorpion toxin AaH2.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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