@article{MTMT:2964742, title = {Timing of CFTR Pore Opening and Structure of Its Transition State.}, url = {https://m2.mtmt.hu/api/publication/2964742}, author = {Sorum, Ben and Czégé, Dávid and Csanády, László}, doi = {10.1016/j.cell.2015.09.052}, journal-iso = {CELL}, journal = {CELL}, volume = {163}, unique-id = {2964742}, issn = {0092-8674}, abstract = {In CFTR, the chloride ion channel mutated in cystic fibrosis (CF) patients, pore opening is coupled to ATP-binding-induced dimerization of two cytosolic nucleotide binding domains (NBDs) and closure to dimer disruption following ATP hydrolysis. CFTR opening rate, unusually slow because of its high-energy transition state, is further slowed by CF mutation DeltaF508. Here, we exploit equilibrium gating of hydrolysis-deficient CFTR mutant D1370N and apply rate-equilibrium free-energy relationship analysis to estimate relative timing of opening movements in distinct protein regions. We find clear directionality of motion along the longitudinal protein axis and identify an opening transition-state structure with the NBD dimer formed but the pore still closed. Thus, strain at the NBD/pore-domain interface, the DeltaF508 mutation locus, underlies the energetic barrier for opening. Our findings suggest a therapeutic opportunity to stabilize this transition-state structure pharmacologically in DeltaF508-CFTR to correct its opening defect, an essential step toward restoring CFTR function.}, year = {2015}, eissn = {1097-4172}, pages = {724-733}, orcid-numbers = {Sorum, Ben/0000-0001-6742-1094; Czégé, Dávid/0000-0001-7746-5816; Csanády, László/0000-0002-6547-5889} } @article{MTMT:1493081, title = {Strict coupling between CFTR's catalytic cycle and gating of its Cl- ion pore revealed by distributions of open channel burst durations}, url = {https://m2.mtmt.hu/api/publication/1493081}, author = {Csanády, László and Vergani, P and Gadsby, DC}, doi = {10.1073/pnas.0911061107}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {107}, unique-id = {1493081}, issn = {0027-8424}, year = {2010}, eissn = {1091-6490}, pages = {1241-1246}, orcid-numbers = {Csanády, László/0000-0002-6547-5889} } @article{MTMT:1493077, title = {Involvement of F1296 and N1303 of CFTR in induced-fit conformational change in response to ATP binding at NBD2}, url = {https://m2.mtmt.hu/api/publication/1493077}, author = {Szöllősi, András and Vergani, P and Csanády, László}, doi = {10.1085/jgp.201010434}, journal-iso = {J GEN PHYSIOL}, journal = {JOURNAL OF GENERAL PHYSIOLOGY}, volume = {136}, unique-id = {1493077}, issn = {0022-1295}, year = {2010}, eissn = {1540-7748}, pages = {407-423}, orcid-numbers = {Szöllősi, András/0000-0002-5570-4609; Csanády, László/0000-0002-6547-5889} } @article{MTMT:1493092, title = {Rapid kinetic analysis of multichannel records by a simultaneous fit to all dwell-time histograms}, url = {https://m2.mtmt.hu/api/publication/1493092}, author = {Csanády, László}, doi = {10.1016/S0006-3495(00)76636-7}, journal-iso = {BIOPHYS J}, journal = {BIOPHYSICAL JOURNAL}, volume = {78}, unique-id = {1493092}, issn = {0006-3495}, year = {2000}, eissn = {1542-0086}, pages = {785-799}, orcid-numbers = {Csanády, László/0000-0002-6547-5889} }