A Shaker K+ Channel with a Miniature Engineered Voltage Sensor

Voltage-gated ion channels sense transmembrane voltage changes via a paddle-shaped motif that includes the C-terminal part of the third transmembrane segment (S3b) and the N-terminal part of the fourth segment (NTS4) that harbors voltage-sensing arginines. Here, we find that residue triplets in S3b and NTS4 can be deleted individually, or even in some combinations, without compromising the channelsʹ basic voltage-gating capability. Thus, a high degree of complementarity between these S3b and NTS4 regions is not required for basic voltage gating per se. Remarkably, the voltage-gated Shaker K+ channel remains voltage gated after a 43 residue paddle sequence is replaced by a glycine triplet. Therefore, the paddle motif comprises a minimal core that suffices to confer voltage gating in the physiological voltage range, and a larger, modulatory part. Our study also shows that the hydrophobic residues between the voltage-sensing arginines help set the sensorʹs characteristic chemical equilibrium between activated and deactivated states.