Phospholipids as a Structural and Functional Determinant for Voltage Sensors in a Kv Channel

Abstract

Recent studies proposed that phosphodiester groups in a phospholipid bilayer help stabilize a voltage sensor in its activated conformation. However, the nature of such channel-lipid interaction is unclear. We are studying the structure and function of the KvAP channel in lipid bilayers. We obtain the structural information of the channel in membranes by electron crystallographic study of two-dimensional crystals, and utilize both biochemical assays and electrical recordings to determine the conformational states of the voltage sensors and the pore domain in reconstituted channels. Our electron crystallographic studies start to reveal that the KvAP voltage sensors in a phospholipid membrane can take an alternative conformation, which is different from the expected four-helix bundle structure observed in the X-ray crystallographic studies of Kv channel proteins in detergents or mixed detergent/lipid micelles. The functional implications of such a new conformation of the voltage sensor are being investigated. Our functional studies converge to the conclusion that annular phospholipids around the channel are required for its voltage sensors to switch from the deactivated to the activated state. Our data suggest that a phospholipid bilayer may be an essential factor for the structure and function of a voltage sensor.