Allosteric mechanism for KCNE1 modulation of KCNQ1 potassium channel activation.

The function of the voltage-gated KCNQ1 potassium channel is regulated by co-assembly with KCNE auxiliary subunits. KCNQ1-KCNE1 channels generate the slow delayed rectifier current, IKs, which contributes to the repolarization phase of the cardiac action potential. A three amino acid motif (F57-T58-L59, FTL) in KCNE1 is essential for slow activation of KCNQ1-KCNE1 channels. However, how this motif interacts with KCNQ1 to control its function is unknown. Combining computational modeling with electrophysiological studies, we developed structural models of the KCNQ1-KCNE1 complex that suggest how KCNE1 controls KCNQ1 activation. The FTL motif binds at a cleft between the voltage-sensing and pore domains and appears to affect the channel gate by an allosteric mechanism. Comparison with the KCNQ1-KCNE3 channel structure suggests a common transmembrane-binding mode for different KCNEs and illuminates how specific differences in the interaction of their triplet motifs determine the profound differences in KCNQ1 functional modulation by KCNE1 versus KCNE3.

Kuenze G ，Vanoye CG ，Desai RR ，Adusumilli S ，Brewer KR ，Woods H ，McDonald EF ，Sanders CR ，George AL Jr ，Meiler J ... -  《eLife》

KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions.

Barro-Soria R ，Ramentol R ，Liin SI ，Perez ME ，Kass RS ，Larsson HP ... -  《-》

KCNE variants reveal a critical role of the beta subunit carboxyl terminus in PKA-dependent regulation of the IKs potassium channel.

Kurokawa J ，Bankston JR ，Kaihara A ，Chen L ，Furukawa T ，Kass RS ... -  《-》

Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels.

Yu H ，Lin Z ，Mattmann ME ，Zou B ，Terrenoire C ，Zhang H ，Wu M ，McManus OB ，Kass RS ，Lindsley CW ，Hopkins CR ，Li M ... -  《-》

KCNE4 domains required for inhibition of KCNQ1.

Manderfield LJ ，Daniels MA ，Vanoye CG ，George AL Jr ... -  《-》