Fig. 4: Mechanistic double-mutant cycle at the α4–α6 interface.
From: Mechanism of pore opening in the calcium-activated chloride channel TMEM16A
a Relation between Ile 551 and Gln 649 in Ca2+-free and -bound conformations. Representation is as in Fig. 3a. b–d Equilibrium constants for mutants at the interface for transitions b, L32, c, L21, and d, L10. Bars indicate the best-fit values of the averaged data shown in Supplementary Fig. 7d (Q649A, n = 7; Q649L, n = 7; I551A/Q649A, n = 8; I551A/Q649L, n = 7). Errors are 95% confidence intervals. e Coupling energy (Gcoupling) and f independent energetic contribution (Gindep) of the indicated residues. Bars indicate quantities calculated using e, Eqs. 31–32, 35 and f, Eq. 34 from the best-fit values shown in b–d. Errors correspond to standard errors. Asterisks indicate significant deviation from zero in a two-sided one-sample t-test (e I551/Q649: ***p = 2e−7 and ***p = 3e−5; I551/L649: ***p = 5e−6 and *p = 0.023; f ***p = 1e−7, ***p = 6e−4, and ***p = 0.001).
