6w6o

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Current revision (06:01, 20 January 2021) (edit) (undo)
 
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==NaChBac-Nav1.7VSDII chimera and HWTX-IV complex==
==NaChBac-Nav1.7VSDII chimera and HWTX-IV complex==
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<StructureSection load='6w6o' size='340' side='right'caption='[[6w6o]]' scene=''>
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<StructureSection load='6w6o' size='340' side='right'caption='[[6w6o]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W6O OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W6O FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6w6o]] is a 8 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=6W6O OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W6O FirstGlance]. <br>
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</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=6w6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w6o OCA], [http://pdbe.org/6w6o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w6o RCSB], [http://www.ebi.ac.uk/pdbsum/6w6o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w6o ProSAT]</span></td></tr>
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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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<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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6w6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w6o OCA], [http://pdbe.org/6w6o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w6o RCSB], [http://www.ebi.ac.uk/pdbsum/6w6o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w6o ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/TXH4_CYRSC TXH4_CYRSC]] This lethal neurotoxin (without cyclization at position 53) inhibits neuronal voltage-gated sodium channel Nav1.2/SCN2A (IC(50)=10-150 nM), rNav1.3/SCN3A (IC(50)=338 nM), Nav1.6/SCN8A (IC(50)=117 nM), and hNav1.7/SCN9A (IC(50)=9.6-33 nM) (PubMed:18628201, PubMed:20855463, PubMed:25658507, PubMed:29703751,PubMed:31234412, PubMed:23760503). It inhibits activation of sodium channel by trapping the voltage sensor of domain II (DIIS4) in the closed configuration (PubMed:18628201, PubMed:23760503). The toxin neither shifts the Nav1.7/SCN9A activation curve nor modifies the slope factor (PubMed:20855463). It does not slow fast-inactivation of hNav1.7/SCN9A channels (PubMed:20855463). In addition, it has only a weak affinity for lipid membranes (PubMed:18054060, PubMed:29703751, PubMed:28115115). This toxin also exists with a pyroglutamate at position 53 (PubMed:23826086). The sole difference observed between modified (mHwTx-IV) and unmodified toxins is that moderate or high depolarization voltages (200 mV) permit the unmodified toxin to dissociate, whereas mHwTx-IV toxin does not dissociate, even at high depolarization voltages (PubMed:23826086). These data indicate that mHwTx-IV strongly binds to voltage sensor of sodium channel even at extreme depolarization voltages (PubMed:23826086).<ref>PMID:12228241</ref> <ref>PMID:18054060</ref> <ref>PMID:18628201</ref> <ref>PMID:20855463</ref> <ref>PMID:21659528</ref> <ref>PMID:23523779</ref> <ref>PMID:23760503</ref> <ref>PMID:25658507</ref> <ref>PMID:28115115</ref> <ref>PMID:29483648</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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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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 6w6o" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
[[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: Nachbac]]
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[[Category: Sodium ion-selective]]
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[[Category: Transport protein-toxin complex]]

Current revision

NaChBac-Nav1.7VSDII chimera and HWTX-IV complex

PDB ID 6w6o

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