The H1348A mutation stabilizes the open state of CFTR in the nonhydrolytic K1250R background. (A) Representative normalized decay time courses of macroscopic currents for H1348A/K1250R and T460S/H1348A/K1250R CFTR after the removal of 2 mM ATP (gray). Solid blue and green lines are fitted exponentials; mean ± SEM relaxation time constants (τrelaxation) are shown in the inset. (B) Thermodynamic mutant cycle for target pair T460-H1348 built on nonhydrolytic closing rates (1/τrelaxation). The top two corners of the mutant cycle were taken from Fig. 5 B. (C) Noise analysis for estimation of Po for H1348A (blue symbols) and T460S/H1348A (green symbols); each symbol represents one patch. (D; left) Mean ± SEM Po for H1348A (blue bar) and T460S/H1348A (green bar). (Right) Thermodynamic mutant cycle for target pair T460-H1348 built on Keq = Po/(1−Po) values under nonhydrolytic conditions. The top two corners of the mutant cycle were taken from Fig. 5 D.
