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Atomistic design of microbial opsin-based blue-shifted optogenetics tools

Hideaki E. Kato, Motoshi Kamiya, Seiya Sugo, Jumpei Ito, Reiya Taniguchi, Ayaka Orito, Kunio Hirata, Ayumu Inutsuka, Akihiro Yamanaka, Andrés D. Maturana, Ryuichiro Ishitani, Yuki Sudo, Shigehiko Hayashi () and Osamu Nureki ()
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Hideaki E. Kato: Graduate School of Science, The University of Tokyo
Motoshi Kamiya: Graduate School of Science, Kyoto University
Seiya Sugo: Graduate School of Science, Kyoto University
Jumpei Ito: Graduate School of Bioagricultural Sciences, Nagoya University
Reiya Taniguchi: Graduate School of Science, The University of Tokyo
Ayaka Orito: Graduate School of Bioagricultural Sciences, Nagoya University
Kunio Hirata: RIKEN SPring-8 Center
Ayumu Inutsuka: Research Institute of Environmental Medicine, Nagoya University
Akihiro Yamanaka: Research Institute of Environmental Medicine, Nagoya University
Andrés D. Maturana: Graduate School of Bioagricultural Sciences, Nagoya University
Ryuichiro Ishitani: Graduate School of Science, The University of Tokyo
Yuki Sudo: Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Shigehiko Hayashi: Graduate School of Science, Kyoto University
Osamu Nureki: Graduate School of Science, The University of Tokyo

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract Microbial opsins with a bound chromophore function as photosensitive ion transporters and have been employed in optogenetics for the optical control of neuronal activity. Molecular engineering has been utilized to create colour variants for the functional augmentation of optogenetics tools, but was limited by the complexity of the protein–chromophore interactions. Here we report the development of blue-shifted colour variants by rational design at atomic resolution, achieved through accurate hybrid molecular simulations, electrophysiology and X-ray crystallography. The molecular simulation models and the crystal structure reveal the precisely designed conformational changes of the chromophore induced by combinatory mutations that shrink its π-conjugated system which, together with electrostatic tuning, produce large blue shifts of the absorption spectra by maximally 100 nm, while maintaining photosensitive ion transport activities. The design principle we elaborate is applicable to other microbial opsins, and clarifies the underlying molecular mechanism of the blue-shifted action spectra of microbial opsins recently isolated from natural sources.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8177

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DOI: 10.1038/ncomms8177

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