Transient receptor potential ankyrin 1 (TRPA1) is a temperature-sensitive ion channel activated by various pungent and irritant compounds that can produce pain in humans. Its activation involves an allosteric mechanism whereby electrophilic agonists evoke interactions within cytosolic domains and open the channel pore through an integrated nexus formed by intracellular membrane proximal regions that are densely packed beneath the lower segment of the S1–S4 sensor domain. Studies indicate that this part of the channel may contain residues that form a water-accessible cavity that undergoes changes in solvation during channel gating. We identified conserved polar residues facing the putative lower crevice of the sensor domain that were crucial determinants of the electrophilic, voltage, and calcium sensitivity of the TRPA1 channel. This part of the sensor may also comprise a domain capable of binding to membrane phosphoinositides through which gating of the channel is regulated in a state-dependent manner.

瞬态受体电位锚蛋白1（TRPA1）是由各种刺激性和刺激性化合物激活的温度敏感离子通道，这些化合物可能在人体内产生疼痛。它的激活涉及一种变构机制，亲电激动剂引起细胞溶质域内的相互作用，并通过由紧密包裹在S1–S4传感器域下部下方的细胞内膜近端区域形成的整合联系打开通道孔。研究表明，通道的这一部分可能包含残留物，这些残留物会形成水可进入的腔，在通道门控过程中溶剂化会发生变化。我们确定了保守的极性残基面对传感器域的较低缝隙，这是TRPA1通道的亲电性，电压和钙敏感性的关键决定因素。