TY  - JOUR
AU  - Sorum, Ben
AU  - Czégé, Dávid
AU  - Csanády, László
TI  - Timing of CFTR Pore Opening and Structure of Its Transition State.
JF  - CELL
J2  - CELL
VL  - 163
PY  - 2015
IS  - 3
SP  - 724
EP  - 733
PG  - 10
SN  - 0092-8674
DO  - 10.1016/j.cell.2015.09.052
UR  - https://m2.mtmt.hu/api/publication/2964742
ID  - 2964742
AB  - 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.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Csanády, László
AU  - Vergani, P
AU  - Gadsby, DC
TI  - Strict coupling between CFTR's catalytic cycle and gating of its Cl- ion pore revealed by distributions of open channel burst durations
JF  - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
J2  - P NATL ACAD SCI USA
VL  - 107
PY  - 2010
IS  - 3
SP  - 1241
EP  - 1246
PG  - 6
SN  - 0027-8424
DO  - 10.1073/pnas.0911061107
UR  - https://m2.mtmt.hu/api/publication/1493081
ID  - 1493081
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Szöllősi, András
AU  - Vergani, P
AU  - Csanády, László
TI  - Involvement of F1296 and N1303 of CFTR in induced-fit conformational change in response to ATP binding at NBD2
JF  - JOURNAL OF GENERAL PHYSIOLOGY
J2  - J GEN PHYSIOL
VL  - 136
PY  - 2010
IS  - 4
SP  - 407
EP  - 423
PG  - 17
SN  - 0022-1295
DO  - 10.1085/jgp.201010434
UR  - https://m2.mtmt.hu/api/publication/1493077
ID  - 1493077
N1  - Department of Medical Biochemistry, Semmelweis University, Budapest H-1094, Hungary            
            Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 7HY, United Kingdom            
            Cited By :17            
            Export Date: 9 March 2022            
            CODEN: JGPLA            
            Correspondence Address: Csanády, L.; Department of Medical Biochemistry, , Budapest H-1094, Hungary; email: laszlo.csanady@eok.sote.hu            
            Chemicals/CAS: adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; Adenosine Triphosphate, 56-65-5; Cystic Fibrosis Transmembrane Conductance Regulator, 126880-72-6            
            Funding details: Medical Research Council, MRC, G0501200
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Csanády, László
TI  - Rapid kinetic analysis of multichannel records by a simultaneous fit to all dwell-time histograms
JF  - BIOPHYSICAL JOURNAL
J2  - BIOPHYS J
VL  - 78
PY  - 2000
IS  - 2
SP  - 785
EP  - 799
PG  - 15
SN  - 0006-3495
DO  - 10.1016/S0006-3495(00)76636-7
UR  - https://m2.mtmt.hu/api/publication/1493092
ID  - 1493092
LA  - English
DB  - MTMT
ER  -