Intracellular cavity of sensor domain controls allosteric gating of TRPA1 channel
| Autor: | Vlastimil Zima, Anna Kadkova, Ivan Barvík, Viktorie Vlachova, Lucie Zimova, Lenka Vyklicka, Viktor Sinica |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation Allosteric regulation Sequence Homology Gating Biochemistry Membrane Potentials 03 medical and health sciences Transient receptor potential channel 0302 clinical medicine Allosteric Regulation Protein Domains Ankyrin Humans Amino Acid Sequence Molecular Biology TRPA1 Cation Channel Ion channel chemistry.chemical_classification Cell Biology Cytosol 030104 developmental biology Membrane HEK293 Cells chemistry Mutation Biophysics Mutagenesis Site-Directed Calcium Ion Channel Gating 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Science signaling. 11(514) |
| ISSN: | 1937-9145 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|