Fig. 6: The potential activation mechanism of HN37.

a The 3D reconstruction and the cartoon model of KCNQ2-CaM_PIP2-HN37. b The binding site of PIP₂ and HN37_A in KCNQ2. Side chains of residues in KCNQ2 involved in the interactions with PIP₂ are shown as sticks. c The open activation gate of KCNQ2-CaM_PIP2-HN37. The dashed lines show diagonal atom-to-atom distance (in Å) at the constriction-lining residues Gly310, Ser314, and Leu318. d Overlay of the pore domains of KCNQ2-CaM_HN37 (green) and KCNQ2-CaM_PIP2-HN37 (orange) structures showing the conformational change in the ion-conducting pathway. The S6 helix bends outward upon PIP₂ binding at the point of PAG segment. e HN37_B and the hydrophobic tails of PIP₂ occupy the same site in KCNQ2 by overlay of KCNQ2-CaM_PIP2-HN37 (orange) and KCNQ2-CaM_HN37 (green). f Structural comparison of VSDs from KCNQ2-CaM _PIP2-HN37 and KCNQ2-CaM_HN37 (green) when the whole channels are aligned. g The proposed HN37 and PIP₂ activation mechanism of KCNQ2 in vivo. h The proposed HN37 and PIP₂ activation model of KCNQ2 in vitro.