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Atomistic design of microbial opsin-based blue-shifted optogenetics tools
Hideaki E Kato1, Motoshi Kamiya2, Seiya Sugo2
1Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Nature Communications
|May 16, 2015
Summary
Scientists engineered blue-shifted microbial opsins for optogenetics. This advancement in optical control of neuronal activity was achieved through rational design and molecular simulations, enhancing photosensitive ion transport capabilities.
Area of Science:
- Biophysics
- Molecular Biology
- Neuroscience
Background:
- Microbial opsins are photosensitive ion transporters crucial for optogenetics.
- Molecular engineering of opsins has created color variants, but protein-chromophore interactions pose challenges.
Purpose of the Study:
- To develop blue-shifted color variants of microbial opsins through rational design.
- To enhance optogenetic tools by improving spectral properties while maintaining function.
Main Methods:
- Hybrid molecular simulations at atomic resolution.
- Electrophysiology to assess ion transport activity.
- X-ray crystallography to determine structural changes.
Main Results:
- Rational design yielded blue-shifted microbial opsins with absorption spectra shifted by up to 100 nm.
- Mutations shrinking the chromophore's π-conjugated system and electrostatic tuning caused the spectral shift.
- Photosensitive ion transport activities were successfully maintained.
Conclusions:
- A design principle for blue-shifted microbial opsins was established.
- The study clarifies the molecular mechanisms behind blue-shifted opsin spectra.
- This approach is applicable to other microbial opsins and natural variants.

