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Science. 2014 Apr 25;344(6182):420-4. doi: 10.1126/science.1252367.

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

Author information

1
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

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.

PMID:
24763591
PMCID:
PMC4096039
DOI:
10.1126/science.1252367
[Indexed for MEDLINE]
Free PMC Article

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