Intracellular cavity of sensor domain controls allosteric gating of TRPA1 channel

0489284 - FGÚ 2019 RIV US eng J - Článek v odborném periodiku
Zímová, Lucie - Sinica, Viktor - Kádková, Anna - Vyklická, Lenka - Zíma, Vlastimil - Barvík, I. - Vlachová, Viktorie
Intracellular cavity of sensor domain controls allosteric gating of TRPA1 channel.
Science Signaling. Roč. 11, č. 514 (2018), č. článku eaan8621. ISSN 1945-0877. E-ISSN 1937-9145
Grant CEP: GA ČR(CZ) GA15-15839S
Institucionální podpora: RVO:67985823
Klíčová slova: TRPA1 * gating * sensor domain * open state * transient receptor potential * ankyrin receptor subtype 1
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 6.565, rok: 2018

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.
Trvalý link: http://hdl.handle.net/11104/0283733