Research ArticleBiochemistry

Intracellular cavity of sensor domain controls allosteric gating of TRPA1 channel

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Sci. Signal.  23 Jan 2018:
Vol. 11, Issue 514, eaan8621
DOI: 10.1126/scisignal.aan8621

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Regulatory cavity in TRPA1

The ion- and voltage-gated channel TRPA1 contributes to acute and chronic pain and itch, as well as vascular function. The channel is sensitive to temperature, pressure, various environmental irritants, and other molecules generated by injury or inflammation in an allosteric manner, meaning that the channel’s response to one stimulus alters its response to another. Zimova et al. investigated the structure of TRPA1 and found an intracellular region within the sensor domain that coordinates this complex allostery. For example, mutations in this cavity prevented stabilization of the channel by interacting intracellular phospholipids, resulting in dysregulated sensitivity to calcium ions. These findings suggest that alterations to the cavity may underlie chronic pain or itch in patients.