| http://purl.uniprot.org/citations/32313203 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32313203 | http://www.w3.org/2000/01/rdf-schema#comment | "Anoctamin-1 (ANO1 or TMEM16A) is a homo-dimeric Ca2+-activated Cl- channel responsible for essential physiological processes. Each monomer harbours a pore and a Ca2+-binding pocket; the voltage-dependent binding of two intracellular Ca2+ ions to the pocket gates the pore. However, in the absence of intracellular Ca2+ voltage activates TMEM16A by an unknown mechanism. Here we show voltage-activated anion currents that are outwardly rectifying, time-independent with fast or absent tail currents that are inhibited by tannic and anthracene-9-carboxylic acids. Since intracellular protons compete with Ca2+ for binding sites in the pocket, we hypothesized that voltage-dependent titration of these sites would induce gating. Indeed intracellular acidification enabled activation of TMEM16A by voltage-dependent protonation, which enhanced the open probability of the channel. Mutating Glu/Asp residues in the Ca2+-binding pocket to glutamine (to resemble a permanent protonated Glu) yielded channels that were easier to activate at physiological pH. Notably, the response of these mutants to intracellular acidification was diminished and became voltage-independent. Thus, voltage-dependent protonation of glutamate/aspartate residues (Glu/Asp) located in the Ca2+-binding pocket underlines TMEM16A activation in the absence of intracellular Ca2+."xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41598-020-62860-9"xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/author | "Arreola J."xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/author | "Perez-Cornejo P."xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/author | "Sanchez-Solano A."xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/author | "Arechiga-Figueroa I.A."xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/author | "De Jesus-Perez J.J."xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/author | "Segura-Covarrubias G."xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/name | "Sci Rep"xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/pages | "6644"xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/title | "Voltage-Dependent Protonation of the Calcium Pocket Enable Activation of the Calcium-Activated Chloride Channel Anoctamin-1 (TMEM16A)."xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/32313203 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32313203 |
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