6nt4

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(New page: '''Unreleased structure''' The entry 6nt4 is ON HOLD Authors: Description: Category: Unreleased Structures)
Current revision (05:42, 28 May 2025) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 6nt4 is ON HOLD
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==Cryo-EM structure of a human-cockroach hybrid Nav channel bound to alpha-scorpion toxin AaH2.==
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<SX load='6nt4' size='340' side='right' viewer='molstar' caption='[[6nt4]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6nt4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Androctonus_australis Androctonus australis], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Periplaneta_americana Periplaneta americana]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6NT4 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=76F:[(2~{R})-3-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-2-octadeca-9,12-dienoyloxy-propyl]+(~{E})-octadec-11-enoate'>76F</scene>, <scene name='pdbligand=AJP:(25R)-2beta,15alpha-dihydroxy-5beta,8alpha,10alpha,14beta,17beta-spirostan-3alpha-yl+beta-D-glucopyranosyl-(1- 3)-beta-D-galactopyranosyl-(1- 2)-[beta-D-xylopyranosyl-(1- 3)]-beta-D-glucopyranosyl-(1- 4)-beta-D-galactopyranoside'>AJP</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nt4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nt4 OCA], [https://pdbe.org/6nt4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nt4 RCSB], [https://www.ebi.ac.uk/pdbsum/6nt4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nt4 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/SCN9A_HUMAN SCN9A_HUMAN] Channelopathy-associated congenital insensitivity to pain;Dravet syndrome;Primary erythromelalgia;Sodium channelopathy-related small fiber neuropathy;Generalized epilepsy with febrile seizures-plus;Hereditary sensory and autonomic neuropathy type 2;Paroxysmal extreme pain disorder;Erythromelalgia. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/SCN9A_HUMAN SCN9A_HUMAN] Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:7720699, PubMed:17167479, PubMed:25240195, PubMed:26680203, PubMed:15385606, PubMed:16988069, PubMed:17145499, PubMed:19369487, PubMed:24311784). It is a tetrodotoxin-sensitive Na(+) channel isoform (PubMed:7720699). Plays a role in pain mechanisms, especially in the development of inflammatory pain (PubMed:17167479, PubMed:17145499, PubMed:19369487, PubMed:24311784).<ref>PMID:15178348</ref> <ref>PMID:15385606</ref> <ref>PMID:16988069</ref> <ref>PMID:17145499</ref> <ref>PMID:17167479</ref> <ref>PMID:19369487</ref> <ref>PMID:24311784</ref> <ref>PMID:25240195</ref> <ref>PMID:26680203</ref> <ref>PMID:7720699</ref> [https://www.uniprot.org/uniprot/SCNA1_PERAM SCNA1_PERAM] Mediates the voltage-dependent sodium ion permeability of excitable membranes.[RuleBase:RU361132]<ref>PMID:28183995</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors:
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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>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 6nt4" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</SX>
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[[Category: Androctonus australis]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Periplaneta americana]]
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[[Category: Clairfeuille T]]
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[[Category: Payandeh J]]
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[[Category: Rohou A]]

Current revision

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

6nt4, resolution 3.50Å

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