6OFA

Wasabi Receptor Toxin

6OFA の概要

• エントリーDOI: 10.2210/pdb6ofa/pdb
• NMR情報: BMRB: 30597
• 分子名称: Wasabi Receptor Toxin (1 entity in total)
• 機能のキーワード: cysteine-stabilized helical hairpin, trpa1, scorpion, venom, toxin
• 由来する生物種: Urodacus manicatus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3862.35

構造登録者

Lin King, J.V.,Kelly, M.J.S.,Julius, D. (登録日: 2019-03-28, 公開日: 2019-08-28, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

SOLUTION NMR