6ofa

From Proteopedia

(Difference between revisions)

Revision as of 10:56, 14 June 2023

Wasabi Receptor Toxin

Structural highlights

6ofa is a 1 chain structure with sequence from Urodacus manicatus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

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^[2]

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

References

↑ Lin King JV, Emrick JJ, Kelly MJS, Herzig V, King GF, Medzihradszky KF, Julius D. A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain. Cell. 2019 Sep 5;178(6):1362-1374.e16. doi: 10.1016/j.cell.2019.07.014. Epub 2019, Aug 22. PMID:31447178 doi:http://dx.doi.org/10.1016/j.cell.2019.07.014
↑ Lin King JV, Emrick JJ, Kelly MJS, Herzig V, King GF, Medzihradszky KF, Julius D. A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain. Cell. 2019 Sep 5;178(6):1362-1374.e16. doi: 10.1016/j.cell.2019.07.014. Epub 2019, Aug 22. PMID:31447178 doi:http://dx.doi.org/10.1016/j.cell.2019.07.014

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/6ofa"

Categories: Large Structures | Urodacus manicatus | Julius D | Kelly MJS | Lin King JV

@@ Line 1: / Line 1: @@
 ==Wasabi Receptor Toxin==
-<StructureSection load='6ofa' size='340' side='right'caption='[[6ofa]], [[NMR_Ensembles_of_Models | 50 NMR models]]' scene=''>
+<StructureSection load='6ofa' size='340' side='right'caption='[[6ofa]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ofa]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OFA FirstGlance]. <br>
+<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='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=6ofa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofa OCA], [http://pdbe.org/6ofa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ofa RCSB], [http://www.ebi.ac.uk/pdbsum/6ofa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofa 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=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 ==
@@ Line 20: / Line 22: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Julius, D]]
+[[Category: Urodacus manicatus]]
-[[Category: Kelly, M J.S]]
+[[Category: Julius D]]
-[[Category: King, J V.Lin]]
+[[Category: Kelly MJS]]
-[[Category: Cysteine-stabilized helical hairpin]]
+[[Category: Lin King JV]]
-[[Category: Scorpion]]
-[[Category: Toxin]]
-[[Category: Trpa1]]
-[[Category: Venom]]

6ofa

From Proteopedia

Revision as of 10:56, 14 June 2023

Wasabi Receptor Toxin

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox