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| | ==Purotoxin-2 NMR structure in DPC micelles== | | ==Purotoxin-2 NMR structure in DPC micelles== |
| - | <StructureSection load='2mzg' size='340' side='right'caption='[[2mzg]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mzg' size='340' side='right'caption='[[2mzg]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mzg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Geoa2 Geoa2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MZG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MZG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mzg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Alopecosa_marikovskyi Alopecosa marikovskyi]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MZG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MZG FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2mzf|2mzf]]</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=2mzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mzg OCA], [https://pdbe.org/2mzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mzg RCSB], [https://www.ebi.ac.uk/pdbsum/2mzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mzg ProSAT]</span></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=2mzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mzg OCA], [http://pdbe.org/2mzg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mzg RCSB], [http://www.ebi.ac.uk/pdbsum/2mzg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mzg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TXPR2_ALOMR TXPR2_ALOMR] Enhances the high-affinity desensitization of human P2RX3 purinoceptors (PubMed:22842000). At 50 nM, the toxin decreases the IC(50) for ambient ATP from 2.67 nM to 0.77 nM in human P2RX3 (PubMed:22842000).<ref>PMID:22842000</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: Geoa2]] | + | [[Category: Alopecosa marikovskyi]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arseniev, A]] | + | [[Category: Arseniev A]] |
| - | [[Category: Grishin, E]] | + | [[Category: Grishin E]] |
| - | [[Category: Nadezhdin, K]] | + | [[Category: Nadezhdin K]] |
| - | [[Category: Oparin, P]] | + | [[Category: Oparin P]] |
| - | [[Category: Vassilevski, A]] | + | [[Category: Vassilevski A]] |
| - | [[Category: Dpc micelle]]
| + | |
| - | [[Category: Module toxin]]
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| - | [[Category: Purotoxin-2]]
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| - | [[Category: Spider venom]]
| + | |
| - | [[Category: Toxin]]
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| Structural highlights
Function
TXPR2_ALOMR Enhances the high-affinity desensitization of human P2RX3 purinoceptors (PubMed:22842000). At 50 nM, the toxin decreases the IC(50) for ambient ATP from 2.67 nM to 0.77 nM in human P2RX3 (PubMed:22842000).[1]
Publication Abstract from PubMed
Traditionally, arachnid venoms are known to contain two particularly important groups of peptide toxins. One is disulfide-rich neurotoxins with a predominance of beta-structure that specifically target protein receptors in neurons or muscle cells. The other is linear cationic cytotoxins that form amphiphilic alpha-helices and exhibit rather non-specific membrane-damaging activity. In the present paper, we describe the first 3D structure of a modular arachnid toxin, purotoxin-2 (PT2) from the wolf spider Alopecosa marikovskyi (Lycosidae), studied by NMR spectroscopy. PT2 is composed of an N-terminal inhibitor cystine knot (ICK, or knottin) beta-structural domain and a C-terminal linear cationic domain. In aqueous solution, the C-terminal fragment is hyper-flexible, whereas the knottin domain is very rigid. In membrane-mimicking environment, the C-terminal domain assumes a stable amphipathic alpha-helix. This helix effectively tethers the toxin to membranes and serves as a membrane-access and membrane-anchoring device. Sequence analysis reveals that the knottin + alpha-helix architecture is quite widespread among arachnid toxins, and PT2 is therefore the founding member of a large family of polypeptides with similar structure motifs. Toxins from this family target different membrane receptors such as P2X in the case of PT2 and calcium channels, but their mechanism of action through membrane access may be strikingly similar.
Structure of purotoxin-2 from wolf spider: modular design and membrane-assisted mode of action in arachnid toxins.,Oparin PB, Nadezhdin KD, Berkut AA, Arseniev AS, Grishin EV, Vassilevski AA Biochem J. 2016 Oct 1;473(19):3113-26. doi: 10.1042/BCJ20160573. Epub 2016 Jul, 13. PMID:27412961[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kabanova NV, Vassilevski AA, Rogachevskaja OA, Bystrova MF, Korolkova YV, Pluzhnikov KA, Romanov RA, Grishin EV, Kolesnikov SS. Modulation of P2X3 receptors by spider toxins. Biochim Biophys Acta. 2012 Nov;1818(11):2868-75. doi: , 10.1016/j.bbamem.2012.07.016. Epub 2012 Jul 25. PMID:22842000 doi:http://dx.doi.org/10.1016/j.bbamem.2012.07.016
- ↑ Oparin PB, Nadezhdin KD, Berkut AA, Arseniev AS, Grishin EV, Vassilevski AA. Structure of purotoxin-2 from wolf spider: modular design and membrane-assisted mode of action in arachnid toxins. Biochem J. 2016 Oct 1;473(19):3113-26. doi: 10.1042/BCJ20160573. Epub 2016 Jul, 13. PMID:27412961 doi:http://dx.doi.org/10.1042/BCJ20160573
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