Show simple item record Sorum, Ben Törőcsik, Beáta Csanády, László 2018-10-17T08:45:06Z 2018-10-17T08:45:06Z 2017
dc.identifier 85032955457
dc.identifier.citation pagination=e29013, pages 17; journalVolume=6; journalTitle=ELIFE;
dc.identifier.uri doi:10.7554/eLife.29013
dc.description.abstract CFTR, the chloride channel mutated in cystic fibrosis (CF) patients, is opened by ATP binding to two cytosolic nucleotide binding domains (NBDs), but pore-domain mutations may also impair gating. ATP-bound NBDs dimerize occluding two nucleotides at interfacial binding sites; one site hydrolyzes ATP, the other is inactive. The pore opens upon tightening, and closes upon disengagement, of the catalytic site following ATP hydrolysis. Extent, timing, and role of non-catalytic-site movements are unknown. Here we exploit equilibrium gating of a hydrolysis-deficient mutant and apply Phi value analysis to compare timing of opening-associated movements at multiple locations, from the cytoplasmic ATP sites to the extracellular surface. Marked asynchrony of motion in the two ATP sites reveals their distinct roles in channel gating. The results clarify the molecular mechanisms of functional cross-talk between canonical and degenerate ATP sites in asymmetric ABC proteins, and of the gating defects caused by two common CF mutations.
dc.relation.ispartof urn:issn:2050-084X
dc.relation.ispartof urn:issn:2050-084X
dc.title Asymmetry of movements in CFTR's two ATP sites during pore opening serves their distinct functions
dc.type Journal Article 2018-08-16T09:18:55Z
dc.language.rfc3066 en
dc.identifier.mtmt 3287727
dc.identifier.wos 000412126300001
dc.identifier.pubmed 28944753
dc.contributor.department SE/AOK/I/OBI/MTA-SE Lendület Ioncsatorna Kutatócsoport
dc.contributor.department SE/AOK/I/Orvosi Biokémiai Intézet
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote FELTÖLTŐ: Bökönyi Zita -

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