Prerequisite Binding Modes Determine the Dynamics of Action of Covalent Agonists of Ion Channel TRPA1.

ABSTRACT: Transient receptor potential ankyrin 1 (TRPA1) is a transmembrane protein channeling the influx of calcium ions. As a polymodal nocisensor, TRPA1 can be activated by thermal, mechanical stimuli and a wide range of chemically damaging molecules including small volatile environmental toxicants and endogenous algogenic lipids. After activation by such compounds, the ion channel opens up, its central pore widens allowing calcium influx into the cytosol inducing signal transduction pathways. Afterwards, the calcium influx desensitizes irritant evoked responses and results in an inactive state of the ion channel. Recent experimental determination of structures of apo and holo forms of TRPA1 opened the way towards the design of new agonists, which can activate the ion channel. The present study i

SUBMITTER: Zsido BZ 

PROVIDER: S-EPMC8540651 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature