Cryo‐EM structure of the Slo1 potassium channel with the auxiliary γ1 subunit suggests a mechanism for depolarization‐independent activation

Abstract

Mammalian Ca2+‐dependent Slo K+ channels can stably associate with auxiliary γ subunits which fundamentally alter their behavior. By a so far unknown mechanism, the four γ subunits reduce the need for voltage‐dependent activation and, thereby, allow Slo to open independently of an action potential. Here, using cryo‐EM, we reveal how the transmembrane helix of γ1/LRRC26 binds and presumably stabilizes the activated voltage‐sensor domain of Slo1. The activation is further enhanced by an intracellular polybasic stretch which locally changes the charge gradient across the membrane. Our data provide a possible explanation for Slo1 regulation by the four γ subunits and also their different activation efficiencies. This suggests a novel activation mechanism of voltage‐gated ion channels by auxiliary subunits.