Fig. 3: KCNE1-induced structural changes of the KCNQ1 VSD and pore.
From: Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating
a Structural comparison of VSDs among KCNQ1APO, (KCNQ1 + KCNE1)APO, and (KCNQ1 + KCNE1)PIP2. Only S2 and S4 were shown for clarity. Red circles highlight E160/R231 and F167/Q234 interactions in (KCNQ1 + KCNE1)APO, and E160/R237 and F167/H240 interactions in KCNQ1APO and (KCNQ1 + KCNE1)PIP2. Arrows indicate movements of R4, the S4 loop, and the S2 loop. Density maps are shown in transparent gray. b VCF results of KCNQ1 (black) and KCNQ1 + KCNE1 (red). VCF traces recorded at +100 mV and –120 mV were normalized to compare their activation and deactivation. c Normalized fluorescence intensity (F) and conductance (G). The F–V relationships (filled black circles for KCNQ1, and filled red circles for KCNQ1 + KCNE1) were fitted with a double Boltzmann equation (F1 and F2 components, black dotted lines for KCNQ1, and red dotted lines for KCNQ1 + KCNE1), and the G–V relationships were fitted with a single Boltzmann equation (open black circles for KCNQ1, and filled red circles for KCNQ1 + KCNE1). All n ≥ 5. d Cartoon scheme showing that KCNE1 suppresses IO state but enhances AO state. e, f Pore radius analysis of KCNQ1APO, (KCNQ1 + KCNE1)APO, and (KCNQ1 + KCNE1)PIP2 with front and back subunits excluded for clarity. Black and orange dots indicate the residues S349 and G345, respectively. g Structural comparison of the activation gate (S349) between (KCNQ1 + KCNE1)APO and (KCNQ1 + KCNE1)PIP2. h Structural comparison of SF among KCNQ1APO, (KCNQ1 + KCNE1)APO, and (KCNQ1 + KCNE1)PIP2. The s2 K+ binding site was disrupted in (KCNQ1 + KCNE1)PIP2. Density maps are shown in transparent gray. i Representative currents of KCNQ1 and KCNQ1 + KCNE1 in the presence of 100 mM Rb+ or 100 mM K+ extracellular solutions. The dashed lines indicate zero current. Currents were tested at 40 mV for 4 s and then stepped to –60 mV to record tail currents. The Rb+/K+ ratio was 3.3 ± 0.1 for KCNQ1 (n = 6) and 0.6 ± 0.1 for KCNQ1 + KCNE1 (n = 6, P = 3.0E-9 with t-test).
