Fig. 2: The PIP₂- and CBD-bound KCNQ2-CaM structure (KCNQ2-CaM_CBD-PIP2).

a The 3D reconstruction and the cartoon model of KCNQ2-CaM_CBD-PIP2. b The binding site of PIP₂ in KCNQ2. Side chains of residues in KCNQ2 involved in the interactions with PIP₂ are shown as sticks. c Voltage-dependent activation curves of WT KCNQ2 and mutants. Data are presented as mean ± SEM. n values are indicated in (d). d V_1/2 values of WT KCNQ2 and mutants. Data are presented as mean ± SEM. One-way ANOVA with Dunnett’s multiple comparisons test was applied. p and n values compared to WT (n = 12) are p = 0.9379 and n = 7 for R87A, ***p = 0.0003 and n = 7 for R89A, p = 0.1484 and n = 9 for R214A, and **p = 0.0015 and n = 10 for R327A. n represents the number of experiments from individual cells. e Different structure arrangements of CTD and CaM in KCNQ2-CaM_apo and KCNQ2-CaM_CBD-PIP2. S6, S6-HA linker, HA, HB, and HC helices of KCNQ2 are colored in blue, red, cornflower-blue, green, and yellow, respectively. The N-lobe and C-lobe of CaM are shown in wheat and pink, respectively. f Interactions between S6 and HB-HC linker. The dashed lines indicate the salt bridge Arg332-Asp566 and the hydrogen bonds Arg325-Asp563 and His328-Pro561. g Structural comparison of the HA, HB, and HC helices in KCNQ2-CaM_apo (wheat) and KCNQ2-CaM_CBD-PIP2 (salmon) in the top view with TMD and HA/HB from the other three subunits omitted for clarity. The N-terminal residue Val564 of HC rotates by ∼40° from KCNQ2-CaM_apo to KCNQ2-CaM_CBD-PIP2. h Overlay of the pore domains of KCNQ2-CaM_apo (wheat) and KCNQ2-CaM_CBD-PIP2 (salmon) structures showing the conformational change in the ion-conducting pathway. The S6 helix bends outward upon PIP₂ binding at the point of PAG segment. i The open activation gate of KCNQ2-CaM_CBD-PIP2. The dashed lines show diagonal atom-to-atom distance (in Å) at the constriction-lining residues Gly310, Ser314, and Leu318. For (c, d), source data are included in the Source Data file.