Fig. 4: KCNE1 induces helix ↔ loop transitions at the S4–S5 linker and S6, significantly changing the VSD–pore coupling.
From: Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating
a, b Structural comparison of KCNQ1APO, (KCNQ1 + KCNE1)APO, and (KCNQ1 + KCNE1)PIP2 to show three KCNE1-induced helix-to-loop transitions around the S4–S5 linker: M238/L239/H240 (MLH), G246/T247 (GT), and I257/H258/R259/Q260 (IHRQ). These helix-to-loop transitions are preserved during the opening of KCNQ1 + KCNE1. c Structural comparison to show that KCNE1 induces a 5.5 Å downward movement of the N-terminus of the S4–S5 linker. During the opening of KCNQ1 + KCNE1, the S4–S5 linker undergoes a 5.8 Å upward movement (with a 4 Å horizontal expansion). d The S4–S5 linker of KCNQ1 + KCNE3 undergoes 1.4 Å upward movement with minimum horizontal expansion during opening. e S6 sequence alignment of KV channels. The Kink1 motif is conserved across all KVs, and Kink2 is conserved in KCNQ channels. f Evolutionary tree analysis of all domain-swapped KV channel families (KV1–4 and KV7). g KCNE1 induces three helix-to-loop transitions in S6: one at the Kink2, and the other two at the two ends of the S6/HA linker QKHF (QKQR and FNRQI). These loops undergo loop-to-helix transitions during the opening of S6, following the bend-to-open transition at Kink1. h Structural comparison of F332 to show that KCNE1 induces an ~70° rotation (counterclockwise) of the side chain. This rotation is mostly restored during the channel opening. i F332A + KCNE1 currents and G–V relation (V50 = 59.3 ± 3.0 mV, n = 6, P = 1.2E-3 with t-test).
