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| | ==Spatial structure of Hm-3, a membrane-active spider toxin affecting sodium channels== | | ==Spatial structure of Hm-3, a membrane-active spider toxin affecting sodium channels== |
| - | <StructureSection load='2mqu' size='340' side='right' caption='[[2mqu]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mqu' size='340' side='right'caption='[[2mqu]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mqu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Crab_spider Crab spider]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MQU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MQU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mqu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Heriaeus_melloteei Heriaeus melloteei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MQU FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mqu OCA], [http://pdbe.org/2mqu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mqu RCSB], [http://www.ebi.ac.uk/pdbsum/2mqu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mqu ProSAT]</span></td></tr> | + | </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=2mqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mqu OCA], [https://pdbe.org/2mqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mqu RCSB], [https://www.ebi.ac.uk/pdbsum/2mqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mqu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TXHM3_HERML TXHM3_HERML] |
| | <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: Crab spider]] | + | [[Category: Heriaeus melloteei]] |
| - | [[Category: Berkut, A A]] | + | [[Category: Large Structures]] |
| - | [[Category: Grishin, E V]] | + | [[Category: Berkut AA]] |
| - | [[Category: Myshkin, M Y]] | + | [[Category: Grishin EV]] |
| - | [[Category: Paramonov, A S]] | + | [[Category: Myshkin MY]] |
| - | [[Category: Shenkarev, Z O]] | + | [[Category: Paramonov AS]] |
| - | [[Category: Vassilevski, A A]] | + | [[Category: Shenkarev ZO]] |
| - | [[Category: Channel activation]] | + | [[Category: Vassilevski AA]] |
| - | [[Category: Gating modifier]]
| + | |
| - | [[Category: Ick]]
| + | |
| - | [[Category: Inhibitor cystine knot]]
| + | |
| - | [[Category: Spider toxin]]
| + | |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Voltage-gated sodium channel]]
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| Structural highlights
Function
TXHM3_HERML
Publication Abstract from PubMed
We present a structural and functional study of a sodium channel activation inhibitor from crab spider venom. Hm-3 is an insecticidal peptide toxin consisting of 35 amino acid residues from the spider Heriaeus melloteei (Thomisidae). We produced Hm-3 recombinantly in Escherichia coli and determined its structure by NMR spectroscopy. Typical for spider toxins, Hm-3 was found to adopt the so-called "inhibitor cystine knot" or "knottin" fold stabilized by three disulfide bonds. Its molecule is amphiphilic with a hydrophobic ridge on the surface enriched in aromatic residues and surrounded by positive charges. Correspondingly, Hm-3 binds to both neutral and negatively charged lipid vesicles. Electrophysiological studies showed that at a concentration of 1 mum Hm-3 effectively inhibited a number of mammalian and insect sodium channels. Importantly, Hm-3 shifted the dependence of channel activation to more positive voltages. Moreover, the inhibition was voltage-dependent, and strong depolarizing prepulses attenuated Hm-3 activity. The toxin is therefore concluded to represent the first sodium channel gating modifier from an araneomorph spider and features a "membrane access" mechanism of action. Its amino acid sequence and position of the hydrophobic cluster are notably different from other known gating modifiers from spider venom, all of which are described from mygalomorph species. We hypothesize parallel evolution of inhibitor cystine knot toxins from Araneomorphae and Mygalomorphae suborders.
Structure of membrane-active toxin from crab spider Heriaeus melloteei suggests parallel evolution of sodium channel gating modifiers in Araneomorphae and Mygalomorphae.,Berkut AA, Peigneur S, Myshkin MY, Paramonov AS, Lyukmanova EN, Arseniev AS, Grishin EV, Tytgat J, Shenkarev ZO, Vassilevski AA J Biol Chem. 2015 Jan 2;290(1):492-504. doi: 10.1074/jbc.M114.595678. Epub 2014, Oct 28. PMID:25352595[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Berkut AA, Peigneur S, Myshkin MY, Paramonov AS, Lyukmanova EN, Arseniev AS, Grishin EV, Tytgat J, Shenkarev ZO, Vassilevski AA. Structure of membrane-active toxin from crab spider Heriaeus melloteei suggests parallel evolution of sodium channel gating modifiers in Araneomorphae and Mygalomorphae. J Biol Chem. 2015 Jan 2;290(1):492-504. doi: 10.1074/jbc.M114.595678. Epub 2014, Oct 28. PMID:25352595 doi:http://dx.doi.org/10.1074/jbc.M114.595678
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