Fig. 1: A site in KCNQ1 for CP1 interaction.

a PIP₂ (upper) and CP1 (lower) molecules. The head of PIP₂ that was used for molecular similarity calculations is marked with a rectangle. The negatively charged groups of the two molecules are marked with circles. b Left, PIP₂ docked on the KCNQ1 and calmodulin complex. Right, magnified view of PIP₂ (upper) or CP1 (lower) docked on KCNQ1 at the VSD-PD interface, and the residues interacting with PIP₂ or CP1 are indicated. Two neighboring subunits of KCNQ1 are colored sky blue and pink, respectively. The bound calmodulins are colored light gray and tan, respectively. c Mutations alter CP1 effects on KCNQ1 conductance–voltage (G–V) relations. The mutated residues are predicted to interact with CP1 in docking. G–V relations of the wild type (WT) and mutant KCNQ1 in the absence (open symbols) or presence (solid symbols) of 10 µM CP1 are shown. d The effect of 10 µM CP1 on G–V shift in voltage range of WT and mutant KCNQ1 (WT n = 11 and mutant n = 3–7). V_1/2 is the voltage where conductance G is half-maximum, and ΔV_1/2 = V_1/2 (CP1) − V_1/2 (control). *Residues predicted to interact with CP1 in docking. N.C. no current expression. ^#Significantly different from the WT (p ≤ 0.05, Tukey–Kramer ANOVA test). For this and subsequent figures, error bar represents standard error of mean (sem), n ≥ 3 unless specified otherwise. In this and other experiments, except for those indicated otherwise, CP1 was applied to the bath solution.