Molecular mechanism of calcium inhibition in viral channelrhodopsins
Abstract Viral channelrhodopsins (VCR1s) are giant-virus-encoded light-gated channels permeable to monovalent and divalent cations, including Na + and Ca 2+ ions, and inhibited by millimolar Ca 2+ concentrations. Here, we combine X-ray crystallography, time-resolved UV-vis spectroscopy, and ATR-FTIR spectroscopy to investigate molecular mechanisms of ion permeation and Ca 2+ -dependent inhibition in OLPVR1. An atomic resolution structure of OLPVR1 obtained in the presence of 10 mM CaCl 2 and 900 mM NaCl reveals a transient intracellular Ca 2+ binding site near T87 and T88, close to the retinal cofactor. Upon photoactivation, this Ca 2+ ion prevents a key rearrangement of the intracellular gate required for ion translocation, namely the flip of E44, thereby disrupting ion conduction. Instead, illumination leads to the accumulation of Na + ions between E44, S208 and the carbonyl oxygen of retinal-binding residue K204. Our findings reveal the molecular basis of Ca 2+ -dependent inhibition in VCR1s and provide a foundation for engineering enhanced tools for calcium optogenetics.
Authors
- Dmitrii Zabelskii (ORCID: https://orcid.org/0000-0001-6906-975X)
- Hideki Kandori (ORCID: https://orcid.org/0000-0002-4922-1344)
- Valentin Gordeliy (ORCID: https://orcid.org/0000-0001-5782-5896)
- Josef Wachtveitl (ORCID: https://orcid.org/0000-0002-8496-8240)
- Mako Aoyama
- Mikihiro Shibata (ORCID: https://orcid.org/0000-0001-5041-3979)
- Gerrit H. U. Lamm (ORCID: https://orcid.org/0009-0006-6743-2344)
- Siarhei Bukhalovich (ORCID: https://orcid.org/0000-0002-0770-6597)
- Sergey Bukhdruker (ORCID: https://orcid.org/0000-0002-0157-532X)
- Alexander Kuzmin (ORCID: https://orcid.org/0000-0003-3945-3691)
- Vsevolod V. Sudarev (ORCID: https://orcid.org/0000-0001-6681-0442)
- Kota Katayama (ORCID: https://orcid.org/0000-0001-8498-4374)
- Ernst Bamberg (ORCID: https://orcid.org/0000-0002-5411-6207)
Institutions
- Kanazawa University (JP)
- Goethe University Frankfurt (DE)
- Centre National de la Recherche Scientifique (FR)
- Moscow Institute of Physics and Technology (RU)
- Nagoya Institute of Technology (JP)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- CEA Grenoble (FR)
- Life Science Institute (JP)
- Max Planck Institute of Biophysics (DE)
- Institut de Biologie Structurale (FR)
- Université Grenoble Alpes (FR)
- European X-Ray Free-Electron Laser (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-09-16
- DOI
- https://doi.org/10.1038/s41467-026-77716-5
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 0.00