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Cryo-EM structure of a blue-shifted channelrhodopsin from Klebsormidium nitens

Author

Listed:
  • Yuzhu Z. Wang

    (The University of Tokyo)

  • Koki Natsume

    (Nagoya Institute of Technology)

  • Tatsuki Tanaka

    (The University of Tokyo)

  • Shoko Hososhima

    (Nagoya Institute of Technology)

  • Rintaro Tashiro

    (Nagoya Institute of Technology)

  • Fumiya K. Sano

    (The University of Tokyo)

  • Hiroaki Akasaka

    (The University of Tokyo)

  • Satoshi P. Tsunoda

    (Nagoya Institute of Technology)

  • Wataru Shihoya

    (The University of Tokyo)

  • Hideki Kandori

    (Nagoya Institute of Technology
    Nagoya Institute of Technology)

  • Osamu Nureki

    (The University of Tokyo)

Abstract

Channelrhodopsins (ChRs) are light-gated ion channels and invaluable tools for optogenetic applications. Recent developments in multicolor optogenetics, in which different neurons are controlled by multiple colors of light simultaneously, have increased the demand for ChR mutants with more distant absorption wavelengths. Here we report the 2.7 Å-resolution cryo-electron microscopy structure of a ChR from Klebsormidium nitens (KnChR), which is one of the most blue-shifted ChRs. The structure elucidates the 6-s-cis configuration of the retinal chromophore, indicating its contribution to a distinctive blue shift in action spectra. The unique architecture of the C-terminal region reveals its role in the allosteric modulation of channel kinetics, enhancing our understanding of its functional dynamics. Employing a rational approach, we developed mutants with blue-shifted action spectra. Finally, we confirm that UV or deep-blue light can activate KnChR-transfected precultured neurons, expanding its utility in optogenetic applications. Our findings contribute valuable insights to advance optogenetic tools and enable refined capabilities in neuroscience experiments.

Suggested Citation

  • Yuzhu Z. Wang & Koki Natsume & Tatsuki Tanaka & Shoko Hososhima & Rintaro Tashiro & Fumiya K. Sano & Hiroaki Akasaka & Satoshi P. Tsunoda & Wataru Shihoya & Hideki Kandori & Osamu Nureki, 2025. "Cryo-EM structure of a blue-shifted channelrhodopsin from Klebsormidium nitens," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59299-9
    DOI: 10.1038/s41467-025-59299-9
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