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2m9l

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Revision as of 02:01, 10 September 2015

Solution structure of protoxin-1

Structural highlights

2m9l is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2m9o
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[TXPR1_THRPR] Inhibits voltage-gated calcium channels Cav3.1/CACNA1G, voltage-gated potassium channels Kv2.1/KCNB1 and all sodium channels tested (Nav1.2/SCN2A, Nav1.5/SCN5A, Nav1.7/SCN9A, and Nav1.8/SCN10A). Shifts the voltage-dependence of channel activation to more positive potentials. Most potent against Nav1.8/SCN10A.^[1] ^[2]

Publication Abstract from PubMed

BACKGROUND: The venoms of predators have been an excellent source of diverse highly specific peptides targeting ion channels. Here we describe the first known peptide antagonist of the nociceptor ion channel transient receptor potential ankyrin 1 (TRPA1). RESULTS: We constructed a recombinant cDNA library encoding approximately 100 diverse GPI-anchored peptide toxins (t-toxins) derived from spider venoms and screened this library by coexpression in Xenopus oocytes with TRPA1. This screen resulted in identification of protoxin-I (ProTx-I), a 35-residue peptide from the venom of the Peruvian green-velvet tarantula, Thrixopelma pruriens, as the first known high-affinity peptide TRPA1 antagonist. ProTx-I was previously identified as an antagonist of voltage-gated sodium (NaV) channels. We constructed a t-toxin library of ProTx-I alanine-scanning mutants and screened this library against NaV1.2 and TRPA1. This revealed distinct partially overlapping surfaces of ProTx-I by which it binds to these two ion channels. Importantly, this mutagenesis yielded two novel ProTx-I variants that are only active against either TRPA1or NaV1.2. By testing its activity against chimeric channels, we identified the extracellular loops of the TRPA1 S1-S4 gating domain as the ProTx-I binding site. CONCLUSIONS: These studies establish our approach, which we term "toxineering," as a generally applicable method for isolation of novel ion channel modifiers and design of ion channel modifiers with altered specificity. They also suggest that ProTx-I will be a valuable pharmacological reagent for addressing biophysical mechanisms of TRPA1 gating and the physiology of TRPA1 function in nociceptors, as well as for potential clinical application in the context of pain and inflammation.

A tarantula-venom peptide antagonizes the TRPA1 nociceptor ion channel by binding to the S1-S4 gating domain.,Gui J, Liu B, Cao G, Lipchik AM, Perez M, Dekan Z, Mobli M, Daly NL, Alewood PF, Parker LL, King GF, Zhou Y, Jordt SE, Nitabach MN Curr Biol. 2014 Mar 3;24(5):473-83. doi: 10.1016/j.cub.2014.01.013. Epub 2014 Feb, 13. PMID:24530065^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Middleton RE, Warren VA, Kraus RL, Hwang JC, Liu CJ, Dai G, Brochu RM, Kohler MG, Gao YD, Garsky VM, Bogusky MJ, Mehl JT, Cohen CJ, Smith MM. Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry. 2002 Dec 17;41(50):14734-47. PMID:12475222
↑ Priest BT, Blumenthal KM, Smith JJ, Warren VA, Smith MM. ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels. Toxicon. 2007 Feb;49(2):194-201. Epub 2006 Sep 27. PMID:17087985 doi:http://dx.doi.org/10.1016/j.toxicon.2006.09.014
↑ Gui J, Liu B, Cao G, Lipchik AM, Perez M, Dekan Z, Mobli M, Daly NL, Alewood PF, Parker LL, King GF, Zhou Y, Jordt SE, Nitabach MN. A tarantula-venom peptide antagonizes the TRPA1 nociceptor ion channel by binding to the S1-S4 gating domain. Curr Biol. 2014 Mar 3;24(5):473-83. doi: 10.1016/j.cub.2014.01.013. Epub 2014 Feb, 13. PMID:24530065 doi:http://dx.doi.org/10.1016/j.cub.2014.01.013

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2m9l"

Categories: Daly, N | Beta hairpin | Toxin

@@ Line 4: / Line 4: @@
 <table><tr><td colspan='2'>[[2m9l]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M9L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M9L FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m9o|2m9o]]</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=2m9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m9l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2m9l RCSB], [http://www.ebi.ac.uk/pdbsum/2m9l PDBsum]</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=2m9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m9l OCA], [http://pdbe.org/2m9l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m9l RCSB], [http://www.ebi.ac.uk/pdbsum/2m9l PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2m9l" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2m9l

From Proteopedia

Revision as of 02:01, 10 September 2015

Solution structure of protoxin-1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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