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Structure-guided transformation of channelrhodopsin into a light-activated chloride channel.

ABSTRACT: Using light to silence electrical activity in targeted cells is a major goal of optogenetics. Available optogenetic proteins that directly move ions to achieve silencing are inefficient, pumping only a single ion per photon across the cell membrane rather than allowing many ions per photon to flow through a channel pore. Building on high-resolution crystal-structure analysis, pore vestibule modeling, and structure-guided protein engineering, we designed and characterized a class of channelrhodopsins (originally cation-conducting) converted into chloride-conducting anion channels. These tools enable fast optical inhibition of action potentials and can be engineered to display step-function kinetics for stable inhibition, outlasting light pulses and for orders-of-magnitude-greater light sensitivity of inhibited cells. The resulting family of proteins defines an approach to more physiological, efficient, and sensitive optogenetic inhibition.

SUBMITTER: Berndt A

PROVIDER: S-EPMC4096039 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Structure-guided transformation of channelrhodopsin into a light-activated chloride channel.

Berndt Andre A Lee Soo Yeun SY Ramakrishnan Charu C Deisseroth Karl K

Science (New York, N.Y.) 20140401 6182

Using light to silence electrical activity in targeted cells is a major goal of optogenetics. Available optogenetic proteins that directly move ions to achieve silencing are inefficient, pumping only a single ion per photon across the cell membrane rather than allowing many ions per photon to flow through a channel pore. Building on high-resolution crystal-structure analysis, pore vestibule modeling, and structure-guided protein engineering, we designed and characterized a class of channelrhodop ...[more]

PMID: 24763591

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