Voltage Sensor of Kv1.2: Structural Basis of Electromechanical Coupling

TLDR

Voltage‑dependent ion channels use voltage sensors to switch between nonconductive and conductive states over a few hundredths of a volt. The study aimed to uncover how these voltage sensors detect membrane voltage. This was achieved by determining the X‑ray crystal structure of a mammalian Shaker family potassium ion channel. The structure revealed that voltage sensors are independent domains that mechanically drive pore opening via S4‑S5 linkers, with two conserved Arg residues on S4 exposed to lipid and two buried, offering a simple model for voltage‑dependent open probability.

Abstract

Voltage-dependent ion channels contain voltage sensors that allow them to switch between nonconductive and conductive states over the narrow range of a few hundredths of a volt. We investigated the mechanism by which these channels sense cell membrane voltage by determining the x-ray crystal structure of a mammalian Shaker family potassium ion (K + ) channel. The voltage-dependent K + channel Kv1.2 grew three-dimensional crystals, with an internal arrangement that left the voltage sensors in an apparently native conformation, allowing us to reach three important conclusions. First, the voltage sensors are essentially independent domains inside the membrane. Second, they perform mechanical work on the pore through the S4-S5 linker helices, which are positioned to constrict or dilate the S6 inner helices of the pore. Third, in the open conformation, two of the four conserved Arg residues on S4 are on a lipid-facing surface and two are buried in the voltage sensor. The structure offers a simple picture of how membrane voltage influences the open probability of the channel.