Identification of Functionally Important Residues of the Rat P2X4 Receptor by Alanine Scanning Mutagenesis of the Dorsal Fin and Left Flipper Domains

0435732 - FGÚ 2015 RIV US eng J - Článek v odborném periodiku
Tvrdoňová, Vendula - Rokic, Milos Boro - Stojilkovic, S. S. - Zemková, Hana
Identification of Functionally Important Residues of the Rat P2X4 Receptor by Alanine Scanning Mutagenesis of the Dorsal Fin and Left Flipper Domains.
PLoS ONE. Roč. 9, č. 11 (2014), e112902. ISSN 1932-6203. E-ISSN 1932-6203
Grant CEP: GA ČR(CZ) GBP304/12/G069; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) EE2.3.30.0025
Grant ostatní: Univerzita Karlova(CZ) 3446/11
Institucionální podpora: RVO:67985823
Klíčová slova: purinergic receptor * P2X * ATP * binding pocket * gating * signal transmission * partial agonists
Kód oboru RIV: ED - Fyziologie
Impakt faktor: 3.234, rok: 2014

Here we focused on the role of left flipper and dorsal fin domains in receptor functions using homomeric rat P2X4 receptor. Alanine scanning mutagenesis of R203-L214 (dorsal fin) and D280-N293 (left flipper) sequences was combined with electrophysiological characterization of P2X4 receptor activity induced by application and withdrawal of ATP and its analogue agonists in the presence and absence of ivermectin, an allosteric regulator of these receptors. These experiments combined with homology modeling indicate that the upper residues of both domains contribute to ATP binding pocket organization and initiation of signal transmission towards bottom residues, and, moreover, left flipper have lead role in desensitization
Trvalý link: http://hdl.handle.net/11104/0239544