6vxo

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<StructureSection load='6vxo' size='340' side='right'caption='[[6vxo]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
<StructureSection load='6vxo' size='340' side='right'caption='[[6vxo]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6vxo]] is a 4 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=6VXO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VXO FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6vxo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Alkalihalobacillus_halodurans_C-125 Alkalihalobacillus halodurans C-125] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VXO FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
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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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BH1501 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vxo OCA], [http://pdbe.org/6vxo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vxo RCSB], [http://www.ebi.ac.uk/pdbsum/6vxo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vxo ProSAT]</span></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=6vxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vxo OCA], [https://pdbe.org/6vxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vxo RCSB], [https://www.ebi.ac.uk/pdbsum/6vxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vxo ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Disease ==
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== Publication Abstract from PubMed ==
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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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NaChBac, the first bacterial voltage-gated Na(+) (Nav) channel to be characterized, has been the prokaryotic prototype for studying the structure-function relationship of Nav channels. Discovered nearly two decades ago, the structure of NaChBac has not been determined. Here we present the single particle electron cryomicroscopy (cryo-EM) analysis of NaChBac in both detergent micelles and nanodiscs. Under both conditions, the conformation of NaChBac is nearly identical to that of the potentially inactivated NavAb. Determining the structure of NaChBac in nanodiscs enabled us to examine gating modifier toxins (GMTs) of Nav channels in lipid bilayers. To study GMTs in mammalian Nav channels, we generated a chimera in which the extracellular fragment of the S3 and S4 segments in the second voltage-sensing domain from Nav1.7 replaced the corresponding sequence in NaChBac. Cryo-EM structures of the nanodisc-embedded chimera alone and in complex with HuwenToxin IV (HWTX-IV) were determined to 3.5 and 3.2 A resolutions, respectively. Compared to the structure of HWTX-IV-bound human Nav1.7, which was obtained at an overall resolution of 3.2 A, the local resolution of the toxin has been improved from approximately 6 to approximately 4 A. This resolution enabled visualization of toxin docking. NaChBac can thus serve as a convenient surrogate for structural studies of the interactions between GMTs and Nav channels in a membrane environment.
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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/Q9KCR8_HALH5 Q9KCR8_HALH5]
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Employing NaChBac for cryo-EM analysis of toxin action on voltage-gated Na(+) channels in nanodisc.,Gao S, Valinsky WC, On NC, Houlihan PR, Qu Q, Liu L, Pan X, Clapham DE, Yan N Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14187-14193. doi:, 10.1073/pnas.1922903117. Epub 2020 Jun 8. PMID:32513729<ref>PMID:32513729</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6vxo" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Alkalihalobacillus halodurans C-125]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Gao, S]]
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[[Category: Gao S]]
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[[Category: Yan, N]]
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[[Category: Yan N]]
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[[Category: Channel]]
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[[Category: Membrane protein]]
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[[Category: Nachbac]]
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[[Category: Sodium ion-selective]]
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Revision as of 14:40, 6 March 2024

NaChBac-Nav1.7VSDII chimera in nanodisc

PDB ID 6vxo

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