6ofa: Difference between revisions
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==Wasabi Receptor Toxin== | |||
<StructureSection load='6ofa' size='340' side='right'caption='[[6ofa]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ofa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Urodacus_manicatus Urodacus manicatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OFA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OFA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 50 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=6ofa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofa OCA], [https://pdbe.org/6ofa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ofa RCSB], [https://www.ebi.ac.uk/pdbsum/6ofa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofa ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KKX1U_UROMN KKX1U_UROMN] Cell-penetrating peptide (CPP) with defensive purpose that induces pain by specifically activating mammalian sensory neuron TRPA1 channels. It non-covalently binds to the same region than other TRPA1 agonists (irritants), but acts via a distinct biochemical mechanism. Its binding stabilizes the TRPA1 open state and diminishes calcium-permeability. Consequently, it produces pain and pain hypersensitivity, but fails to trigger efferent release of neuropeptides (CGRP) and neurogenic inflammation typically produced by noxious electrophiles. Is not active on voltage-gated potassium channels and other TRP channels.<ref>PMID:31447178</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
TRPA1 is a chemosensory ion channel that functions as a sentinel for structurally diverse electrophilic irritants. Channel activation occurs through an unusual mechanism involving covalent modification of cysteine residues clustered within an amino-terminal cytoplasmic domain. Here, we describe a peptidergic scorpion toxin (WaTx) that activates TRPA1 by penetrating the plasma membrane to access the same intracellular site modified by reactive electrophiles. WaTx stabilizes TRPA1 in a biophysically distinct active state characterized by prolonged channel openings and low Ca(2+) permeability. Consequently, WaTx elicits acute pain and pain hypersensitivity but fails to trigger efferent release of neuropeptides and neurogenic inflammation typically produced by noxious electrophiles. These findings provide a striking example of convergent evolution whereby chemically disparate animal- and plant-derived irritants target the same key allosteric regulatory site to differentially modulate channel activity. WaTx is a unique pharmacological probe for dissecting TRPA1 function and its contribution to acute and persistent pain. | |||
A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain.,Lin King JV, Emrick JJ, Kelly MJS, Herzig V, King GF, Medzihradszky KF, Julius D Cell. 2019 Sep 5;178(6):1362-1374.e16. doi: 10.1016/j.cell.2019.07.014. Epub 2019, Aug 22. PMID:31447178<ref>PMID:31447178</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6ofa" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Urodacus manicatus]] | |||
[[Category: Julius D]] | |||
[[Category: Kelly MJS]] | |||
[[Category: Lin King JV]] | |||
