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| | ==Solution structure and alanine scan of a spider toxin that affects the activation of mammalian sodium channels== | | ==Solution structure and alanine scan of a spider toxin that affects the activation of mammalian sodium channels== |
| - | <StructureSection load='2gx1' size='340' side='right' caption='[[2gx1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2gx1' size='340' side='right'caption='[[2gx1]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2gx1]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GX1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2gx1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Macrothele_gigas Macrothele gigas]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GX1 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=2gx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gx1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gx1 RCSB], [http://www.ebi.ac.uk/pdbsum/2gx1 PDBsum]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=2gx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gx1 OCA], [https://pdbe.org/2gx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gx1 RCSB], [https://www.ebi.ac.uk/pdbsum/2gx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gx1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TXMG5_MACGS TXMG5_MACGS]] Insect and vertebrate active toxin. Binds to site 4 of mammalian voltage-gated sodium channels and shifts the activation voltage of the mammalian Nav1.2a/SCN2A channel to more hyperpolarized voltages, whereas the insect channel, DmNav1 (para), is not affected. Competes for binding at site 3 of the insect sodium channel. Causes temporary paralysis when injected into lepidopteran larvae at 8.6 nmol/g. A low intracranial injection dose into mice causes lacrimation, closure of the eyes and sweating. A high injection dose causes extensive lacrimation and death.<ref>PMID:12860384</ref> | + | [https://www.uniprot.org/uniprot/TXMG5_MACGS TXMG5_MACGS] Insect and vertebrate active toxin. Binds to site 4 of mammalian voltage-gated sodium channels and shifts the activation voltage of the mammalian Nav1.2a/SCN2A channel to more hyperpolarized voltages, whereas the insect channel, DmNav1 (para), is not affected. Competes for binding at site 3 of the insect sodium channel. Causes temporary paralysis when injected into lepidopteran larvae at 8.6 nmol/g. A low intracranial injection dose into mice causes lacrimation, closure of the eyes and sweating. A high injection dose causes extensive lacrimation and death.<ref>PMID:12860384</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2gx1" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Billen, B]] | + | [[Category: Large Structures]] |
| - | [[Category: Bosmans, F]] | + | [[Category: Macrothele gigas]] |
| - | [[Category: Corzo, G]] | + | [[Category: Billen B]] |
| - | [[Category: Norton, R S]] | + | [[Category: Bosmans F]] |
| - | [[Category: Sabo, J K]] | + | [[Category: Corzo G]] |
| - | [[Category: Tytgat, J]] | + | [[Category: Norton RS]] |
| - | [[Category: Villegas, E]] | + | [[Category: Sabo JK]] |
| - | [[Category: Spider toxin]] | + | [[Category: Tytgat J]] |
| - | [[Category: Toxin]] | + | [[Category: Villegas E]] |
| Structural highlights
Function
TXMG5_MACGS Insect and vertebrate active toxin. Binds to site 4 of mammalian voltage-gated sodium channels and shifts the activation voltage of the mammalian Nav1.2a/SCN2A channel to more hyperpolarized voltages, whereas the insect channel, DmNav1 (para), is not affected. Competes for binding at site 3 of the insect sodium channel. Causes temporary paralysis when injected into lepidopteran larvae at 8.6 nmol/g. A low intracranial injection dose into mice causes lacrimation, closure of the eyes and sweating. A high injection dose causes extensive lacrimation and death.[1]
Publication Abstract from PubMed
Magi 5, from the hexathelid spider Macrothele gigas, is a 29-residue polypeptide containing three disulfide bridges. It binds specifically to receptor site 4 on mammalian voltage-gated sodium channels and competes with scorpion beta-toxins, such as Css IV from Centruroides suffusus suffusus. As a consequence, Magi 5 shifts the activation voltage of the mammalian rNav1.2a channel to more hyperpolarized voltages, whereas the insect channel, DmNav1, is not affected. To gain insight into toxin-channel interactions, Magi 5 and 23 analogues were synthesized. The three-dimensional structure of Magi 5 in aqueous solution was determined, and its voltage-gated sodium channel-binding surfaces were mapped onto this structure using data from electrophysiological measurements on a series of Ala-substituted analogues. The structure clearly resembles the inhibitor cystine knot structural motif, although the triple-stranded beta-sheet typically found in that motif is partially distorted in Magi 5. The interactive surface of Magi 5 toward voltage-gated sodium channels resembles in some respects the Janus-faced atracotoxins, with functionally important charged residues on one face of the toxin and hydrophobic residues on the other. Magi 5 also resembles the scorpion beta-toxin Css IV, which has distinct nonpolar and charged surfaces that are critical for channel binding and has a key Glu involved in voltage sensor trapping. These two distinct classes of toxin, with different amino acid sequences and different structures, may utilize similar groups of residues on their surface to achieve the common end of modifying voltage-gated sodium channel function.
Solution structure and alanine scan of a spider toxin that affects the activation of mammalian voltage-gated sodium channels.,Corzo G, Sabo JK, Bosmans F, Billen B, Villegas E, Tytgat J, Norton RS J Biol Chem. 2007 Feb 16;282(7):4643-52. Epub 2006 Dec 5. PMID:17148449[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Corzo G, Gilles N, Satake H, Villegas E, Dai L, Nakajima T, Haupt J. Distinct primary structures of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel. FEBS Lett. 2003 Jul 17;547(1-3):43-50. PMID:12860384
- ↑ Corzo G, Sabo JK, Bosmans F, Billen B, Villegas E, Tytgat J, Norton RS. Solution structure and alanine scan of a spider toxin that affects the activation of mammalian voltage-gated sodium channels. J Biol Chem. 2007 Feb 16;282(7):4643-52. Epub 2006 Dec 5. PMID:17148449 doi:M605403200
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