Fig. 2: Asymmetric contributions of degenerate and consensus ATP-binding sites.
From: CFTR function, pathology and pharmacology at single-molecule resolution
a, Schematic of degenerate and consensus sites as viewed from the plasma membrane. b, Steady-state ATP hydrolysis rates for the wild-type CFTR and variants. Data represent means and standard errors for 10 (wild-type), 3 (E1371Q) or 4 (W401A, Y1219 and W401A/Y1219A) measurements. *P = 0.014; ****P = 1.2 × 10−11 (E1371Q), 2.7 × 10−11 (Y1219A) and 2.1 × 10−11 (W401A/Y1219A). c, Sample traces from single-channel electrophysiology (top) and smFRET (bottom) of the CFTR(W401A) variant. The substitution was made in wild-type CFTR and CFTRFRET backgrounds for electrophysiology and smFRET, respectively. In electrophysiology traces, upward deflections correspond to opening. d, Dwell-time distributions of opening and dimerization events for CFTR(W401A). e, As in c, but with the CFTR(Y1219A) variant. f, Dimerization probabilities of wild-type CFTRFRET and variants. Data represent means and standard errors for 8 (wild-type), 4 (E1371Q), 5 (W401A) and 7 (Y1219A) measurements. NS, not significant; ****P = 8.0 × 10−9 (W401A) and 4.4 × 10−11 (Y1219A). g, Open probabilities of CFTR variants. Data represent means and standard errors for 39 (wild-type), 10 (E1371Q), 9 (W401A) and 5 (Y1291A) bilayers. ****P = 10−15 (E1371Q) and 4.9 × 10−5 (Y1219A). h, Coupling ratios of CFTR variants, defined as open probability divided by dimerization probability. Data represent means and standard errors. Phosphorylated CFTR variants at 3 mM ATP were used in all panels. For relevant panels, statistical significance relative to the wild-type was tested by one-way analysis of variance.
