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| | ==Solution structure of VSTx1== | | ==Solution structure of VSTx1== |
| - | <StructureSection load='2n1n' size='340' side='right'caption='[[2n1n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2n1n' size='340' side='right'caption='[[2n1n]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2n1n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Chilean_red-back Chilean red-back]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N1N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2n1n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Grammostola_rosea Grammostola rosea]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N1N FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1s6x|1s6x]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2n1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n1n OCA], [https://pdbe.org/2n1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n1n RCSB], [https://www.ebi.ac.uk/pdbsum/2n1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n1n ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2n1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n1n OCA], [https://pdbe.org/2n1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n1n RCSB], [https://www.ebi.ac.uk/pdbsum/2n1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n1n ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/VSTX1_GRARO VSTX1_GRARO]] Inhibits sodium channels Nav1.7/SCN9A and potassium channels Kv11.1/KCNH2. Also binds the voltage-sensor domain of the potassium channel KvAP (from the archaeon Aeropyrum pernix) with very slow apparent binding kinetics and affects channel gating. Reaches its target by dynamically partitioning into anionic or zwitterionic headgroup lipid membranes. May bind to the open state of KvAP.<ref>PMID:15241419</ref> <ref>PMID:15287735</ref> <ref>PMID:17002285</ref> <ref>PMID:19955179</ref>
| + | [https://www.uniprot.org/uniprot/VSTX1_GRARO VSTX1_GRARO] Inhibits sodium channels Nav1.7/SCN9A and potassium channels Kv11.1/KCNH2. Also binds the voltage-sensor domain of the potassium channel KvAP (from the archaeon Aeropyrum pernix) with very slow apparent binding kinetics and affects channel gating. Reaches its target by dynamically partitioning into anionic or zwitterionic headgroup lipid membranes. May bind to the open state of KvAP.<ref>PMID:15241419</ref> <ref>PMID:15287735</ref> <ref>PMID:17002285</ref> <ref>PMID:19955179</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chilean red-back]] | + | [[Category: Grammostola rosea]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: King, G F]] | + | [[Category: King GF]] |
| - | [[Category: Lau, H Y]] | + | [[Category: Lau HY]] |
| - | [[Category: Mobli, M]] | + | [[Category: Mobli M]] |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
VSTX1_GRARO Inhibits sodium channels Nav1.7/SCN9A and potassium channels Kv11.1/KCNH2. Also binds the voltage-sensor domain of the potassium channel KvAP (from the archaeon Aeropyrum pernix) with very slow apparent binding kinetics and affects channel gating. Reaches its target by dynamically partitioning into anionic or zwitterionic headgroup lipid membranes. May bind to the open state of KvAP.[1] [2] [3] [4]
Publication Abstract from PubMed
Voltage-sensor domains (VSDs) are modular transmembrane domains of voltage-gated ion channels that respond to changes in membrane potential by undergoing conformational changes that are coupled to gating of the ion-conducting pore. Most spider-venom peptides function as gating modifiers by binding to the VSDs of voltage-gated channels and trapping them in a closed or open state. To understand the molecular basis underlying this mode of action, we used nuclear magnetic resonance to delineate the atomic details of the interaction between the VSD of the voltage-gated potassium channel KvAP and the spider-venom peptide VSTx1. Our data reveal that the toxin interacts with residues in an aqueous cleft formed between the extracellular S1-S2 and S3-S4 loops of the VSD whilst maintaining lipid interactions in the gaps formed between the S1-S4 and S2-S3 helices. The resulting network of interactions increases the energetic barrier to the conformational changes required for channel gating, and we propose that this is the mechanism by which gating modifier toxins inhibit voltage-gated ion channels.
Molecular basis of the interaction between gating modifier spider toxins and the voltage sensor of voltage-gated ion channels.,Lau CH, King GF, Mobli M Sci Rep. 2016 Sep 28;6:34333. doi: 10.1038/srep34333. PMID:27677715[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lee SY, MacKinnon R. A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom. Nature. 2004 Jul 8;430(6996):232-5. PMID:15241419 doi:http://dx.doi.org/10.1038/nature02632
- ↑ Ruta V, MacKinnon R. Localization of the voltage-sensor toxin receptor on KvAP. Biochemistry. 2004 Aug 10;43(31):10071-9. PMID:15287735 doi:http://dx.doi.org/10.1021/bi049463y
- ↑ Bemporad D, Sands ZA, Wee CL, Grottesi A, Sansom MS. Vstx1, a modifier of Kv channel gating, localizes to the interfacial region of lipid bilayers. Biochemistry. 2006 Oct 3;45(39):11844-55. PMID:17002285 doi:http://dx.doi.org/10.1021/bi061111z
- ↑ Redaelli E, Cassulini RR, Silva DF, Clement H, Schiavon E, Zamudio FZ, Odell G, Arcangeli A, Clare JJ, Alagon A, de la Vega RC, Possani LD, Wanke E. Target promiscuity and heterogeneous effects of tarantula venom peptides affecting Na+ and K+ ion channels. J Biol Chem. 2010 Feb 5;285(6):4130-42. doi: 10.1074/jbc.M109.054718. Epub 2009, Dec 2. PMID:19955179 doi:http://dx.doi.org/10.1074/jbc.M109.054718
- ↑ Lau CH, King GF, Mobli M. Molecular basis of the interaction between gating modifier spider toxins and the voltage sensor of voltage-gated ion channels. Sci Rep. 2016 Sep 28;6:34333. doi: 10.1038/srep34333. PMID:27677715 doi:http://dx.doi.org/10.1038/srep34333
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