6OFA

Wasabi Receptor Toxin

Summary for 6OFA

• Entry DOI: 10.2210/pdb6ofa/pdb
• NMR Information: BMRB: 30597
• Descriptor: Wasabi Receptor Toxin (1 entity in total)
• Functional Keywords: cysteine-stabilized helical hairpin, trpa1, scorpion, venom, toxin
• Biological source: Urodacus manicatus
• Total number of polymer chains: 1
• Total formula weight: 3862.35

Authors

Lin King, J.V.,Kelly, M.J.S.,Julius, D. (deposition date: 2019-03-28, release date: 2019-08-28, Last modification date: 2024-10-16)

Primary citation

Lin King, J.V.,Emrick, J.J.,Kelly, M.J.S.,Herzig, V.,King, G.F.,Medzihradszky, K.F.,Julius, D.
A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain.
Cell, 178:1362-1374.e16, 2019

PubMed Abstract: 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 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.

PubMed: 31447178
DOI: 10.1016/j.cell.2019.07.014

Experimental method

SOLUTION NMR