7k48

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Current revision (11:04, 23 October 2024) (edit) (undo)
 
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==Structure of NavAb/Nav1.7-VS2A chimera trapped in the resting state by tarantula toxin m3-Huwentoxin-IV==
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<StructureSection load='7k48' size='340' side='right'caption='[[7k48]]' scene=''>
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<StructureSection load='7k48' size='340' side='right'caption='[[7k48]], [[Resolution|resolution]] 3.60&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= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7k48]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Aliarcobacter_butzleri_RM4018 Aliarcobacter butzleri RM4018], [https://en.wikipedia.org/wiki/Cyriopagopus_schmidti Cyriopagopus schmidti], [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] 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=7K48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K48 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=7k48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k48 OCA], [http://pdbe.org/7k48 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7k48 RCSB], [http://www.ebi.ac.uk/pdbsum/7k48 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7k48 ProSAT]</span></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]] 3.6&#8491;</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=7k48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k48 OCA], [https://pdbe.org/7k48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k48 RCSB], [https://www.ebi.ac.uk/pdbsum/7k48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k48 ProSAT]</span></td></tr>
</table>
</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/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.[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/A8EVM5_ALIB4 A8EVM5_ALIB4]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Voltage-gated sodium channels initiate electrical signals and are frequently targeted by deadly gating-modifier neurotoxins, including tarantula toxins, which trap the voltage sensor in its resting state. The structural basis for tarantula-toxin action remains elusive because of the difficulty of capturing the functionally relevant form of the toxin-channel complex. Here, we engineered the model sodium channel Na(V)Ab with voltage-shifting mutations and the toxin-binding site of human Na(V)1.7, an attractive pain target. This mutant chimera enabled us to determine the cryoelectron microscopy (cryo-EM) structure of the channel functionally arrested by tarantula toxin. Our structure reveals a high-affinity resting-state-specific toxin-channel interaction between a key lysine residue that serves as a "stinger" and penetrates a triad of carboxyl groups in the S3-S4 linker of the voltage sensor. By unveiling this high-affinity binding mode, our studies establish a high-resolution channel-docking and resting-state locking mechanism for huwentoxin-IV and provide guidance for developing future resting-state-targeted analgesic drugs.
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Structural Basis for High-Affinity Trapping of the Na(V)1.7 Channel in Its Resting State by Tarantula Toxin.,Wisedchaisri G, Tonggu L, Gamal El-Din TM, McCord E, Zheng N, Catterall WA Mol Cell. 2021 Jan 7;81(1):38-48.e4. doi: 10.1016/j.molcel.2020.10.039. Epub 2020 , Nov 23. PMID:33232657<ref>PMID:33232657</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 7k48" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Maltose-binding protein 3D structures|Maltose-binding protein 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Aliarcobacter butzleri RM4018]]
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[[Category: Cyriopagopus schmidti]]
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[[Category: Escherichia coli K-12]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Catterall WA]]
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[[Category: Gamal El-Din TM]]
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[[Category: McCord E]]
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[[Category: Tonggu L]]
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[[Category: Wisedchaisri G]]
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[[Category: Zheng N]]

Current revision

Structure of NavAb/Nav1.7-VS2A chimera trapped in the resting state by tarantula toxin m3-Huwentoxin-IV

PDB ID 7k48

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