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, Osamu Nureki

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)


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.

Original languageEnglish
Article number7177
JournalNature communications
Publication statusPublished - May 15 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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