Fig. 8: Carnosic acid binds to KCNQ3* S4-5 linker arginines.
a Structure of aloperine. b Mean traces for KCNQ3/5 expressed in oocytes in the absence (Control) or presence of aloperine and/or carnosic acid (5 µM). Scale bars lower left; voltage protocol upper inset; n = 5 per group. c Mean normalized tail current (G/Gmax) for KCNQ3/5, pharmacology as in panel B; n = 5 per group. d Mean unclamped oocyte membrane potential for oocytes expressing KCNQ3/5; pharmacology as in (b); n = 5 per group. e. In silico docking results for aloperine in a KCNQ5 model; carnosic acid in KCNQ2 cryo-EM-derived structure56,57 and in a KCNQ3 AlphaFold model. f Close-up of carnosic acid docking to KCNQ3 model structure showing the predicted ionic bond between the carnosic acid carboxyl group and the R243 guanidinium group (green). g Mean traces for mutant (as indicated) KCNQ3* expressed in oocytes in the absence (Control) or presence of carnosic acid (100 µM). Scale bars lower left; voltage protocol as in (b); n = 4–10 per group. h Mean normalized tail current (G/Gmax) for KCNQ3* mutants in the absence (black) or presence (red) of carnosic acid; n = 4–10 per group. N/A, not applicable. i Mean unclamped oocyte membrane potential for oocytes expressing KCNQ3* mutants in the absence (black) or presence (red) of carnosic acid; n = 4–10 per group. N/A not applicable. j Mean ΔV0.5act versus [carnosic acid] for R242A KCNQ3*; n = 4–10 per group; wild-type KCNQ3* data from Fig. 4 for comparison. k Mean ΔEM versus [carnosic acid] for R242A KCNQ3*; n = 4–10 per group; wild-type KCNQ3* data from Fig. 4 for comparison. Error bars indicate SEM. n indicates number of biologically independent oocytes. Statistical comparisons by one-way ANOVA and paired t-test.
