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.
- MeSH
- alosterická regulace MeSH
- gating iontového kanálu * MeSH
- HEK293 buňky MeSH
- kationtový kanál TRPA1 chemie fyziologie MeSH
- konformace proteinů MeSH
- lidé MeSH
- membránové potenciály * MeSH
- molekulární modely MeSH
- mutace MeSH
- mutageneze cílená MeSH
- proteinové domény MeSH
- sekvence aminokyselin MeSH
- sekvenční homologie MeSH
- vápník metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
