Fig. 6: The KCNE1-induced helix ↔ loop transitions create a fenestration in the IKs channel.
From: Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating
a, b Activation currents and G–V relation of KCNQ1 + KCNE3. G–V relations of KCNQ1 (gray) and KCNQ1 + KCNE1 (red) are also shown. c Cartoon scheme showing that KCNE3 enhances IO state. d Structural comparison of (KCNQ1 + KCNE1)APO and (KCNQ1 + KCNE3)APO (PDB: 6V0032) to show that KCNE1 induces further ~3 Å movement of S1 compared to KCNE3. e Both the VSDs of (KCNQ1 + KCNE3)APO (PDB: 6V00) and (KCNQ1 + KCNE3)PIP2 (PDB: 6V0132) are in activated state. Red circles highlight E160/R237 and F167/H240 interactions. f Structural comparison of the activation gate (S349) between (KCNQ1 + KCNE3)APO (PDB: 6V00) and (KCNQ1 + KCNE3)PIP2 (PDB: 6V0132). g In KCNQ1APO, adjacent S6 segments remain tightly packed (V334 ↔ F340 distance is 7.7 Å). h In (KCNQ1 + KCNE3)APO, no helix-to-loop transition was observed, and adjacent S6 segments remain tightly packed (V334 ↔ F340 distance is 8.8 Å). i In (KCNQ1 + KCNE1)APO, KCNE1-induced helix-to-loop transitions at the FSVFA motifs force S6 helices to separate, creating a fenestration pocket (V334 ↔ F340 distance is 11.3 Å). j Representative activation currents of KCNQ1, KCNQ1 + KCNE1, and F340W + KCNE1 before and after adding 1 μM AC-1.29 To avoid potential inactivation at high voltage, the F340W + KCNE1 channel currents were recorded at 0 mV.51
