Voltage-gated K+ channel activation is proposed to result from simultaneous bending of all S6 segments away from the central axis, enlarging the aperture of the pore sufficiently to permit diffusion of K+ into the water-filled central cavity. The hinge position for the bending motion of each S6 segment is proposed to be a Gly residue and/or a Pro-Val-Pro motif in Kv1-Kv4 channels. The KCNQ1 (Kv7.1) channel has Ala-336 in the Gly-hinge position and Pro-Ala-Gly. Mutation of Ala-336 to Gly, Cys and Thr in KCNQ1 resulted in active channels with a decrease in current amplitude with increased side chain volume. In contrast, mutation of Ala-336 to Pro rendered channels inactive. On the other hand, mutation of the Pro or Gly of the Pro-Ala-Gly motif to Ala abolished KCNQ1 function and introduction of Gly in front of the Ala-mutations partially recovered channel function, suggesting that flexibility at the PAG is important for channel activation. A336-mutation-dependent changes in current amplitude, but not kinetics, were found in heteromeric KCNQ1/KCNE1 channels. We further present data suggesting that binding of KCNE1 to the outer surface of KCNQ1-S5-S6-pore domain changes subunit-subunit interactions to allosterically modify the selectivity filter.