Engineering Light-Regulated Ion Channels

INTRODUCTION

Optical regulation provides unrivaled spatial and temporal precision for the control of protein function. We describe a strategy to engineer photosensitivity onto ion channels based on small photoisomerizable molecules. Photosensitivity is targeted to the ion channel of interest by combining the photoisomerizable moiety with a specific agonist or antagonist. Inclusion of a cysteine-reactive maleimide group enables covalent attachment of the photoswitch to a genetically engineered cysteine on the surface of the ion channel. Exposure to different wavelengths of light triggers changes in the properties of the photoswitch that enable control of protein function.