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Engineering of bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s
Engineering of bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s
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Engineering of bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s
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Engineering of bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s
Engineering of bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s

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Engineering of bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s
Engineering of bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s
Journal Article

Engineering of bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s

2023
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Overview
Optogenetic tools for controlling protein–protein interactions (PPIs) have been developed from a small number of photosensory modules that respond to a limited selection of wavelengths. Cyanobacteriochrome (CBCR) GAF domain variants respond to an unmatched array of colors; however, their natural molecular mechanisms of action cannot easily be exploited for optogenetic control of PPIs. Here we developed bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s by engineering synthetic light-dependent interactors for a red/green GAF domain. The systematic approach enables the future engineering of the broad chromatic palette of CBCRs for optogenetics use. BICYCLs are among the smallest optogenetic tools for controlling PPIs and enable either green-ON/red-OFF (BICYCL-Red) or red-ON/green-OFF (BICYCL-Green) control with up to 800-fold state selectivity. The access to green wavelengths creates new opportunities for multiplexing with existing tools. We demonstrate the utility of BICYCLs for controlling protein subcellular localization and transcriptional processes in mammalian cells and for multiplexing with existing blue-light tools. Bidirectional, cyanobacteriochrome-based light-inducible dimers (BICYCL)s enable optogenetic control of protein–protein interactions with green and red light, allowing multiplexing with existing blue light-controlled tools.