Light-induced conformational switching and magnetic sensitivity of Drosophila cryptochrome
Cryptochromes are light-sensitive flavoproteins with various biological roles, including a proposed function in magnetoreception. This mechanism rests on a magnetically sensitive photochemical reaction of the flavin chromophore with a chain of tryptophan residues within the protein scaffold. However, the protein-mediated mechanisms of magnetic signal transduction are unclear. We have examined the response of an archetypal cryptochrome, DmCRY, to photochemical activation by means of hydrogen-deuterium exchange mass spectrometry, complemented by molecular dynamics simulations and cavity ring-down spectroscopy. We were able to measure the dynamics of DmCRY at near-residue level resolution, revealing a reversible, long-lived, blue-light induced conformational change in the protein's C-terminal tail. This putative signaling state was validated using different illumination conditions, and by examining DmCRY variants in which the electron transfer chain was perturbed. Our results show how the photochemical behavior of the flavin chromophore generates a state of DmCRY that may initiate downstream interactions.
Authors
- Shane A. Chandler
- Guodong Cao (ORCID: https://orcid.org/0000-0003-2854-8951)
- Tilo Zollitsch
- Christiane R. Timmel (ORCID: https://orcid.org/0000-0003-1828-7700)
- Laila M. N. Shah (ORCID: https://orcid.org/0000-0002-6666-6046)
- Ilia A. Solov’yov (ORCID: https://orcid.org/0000-0002-8626-145X)
- Stuart R. Mackenzie (ORCID: https://orcid.org/0000-0002-3166-8631)
- P. J. Hore (ORCID: https://orcid.org/0000-0002-8863-570X)
- Navoneel Sen
- Angela S. Gehrckens
- Justin L. P. Benesch (ORCID: https://orcid.org/0000-0002-1507-3742)
- Ryan Rodriguez
- Stefan Weber (ORCID: https://orcid.org/0000-0003-4090-7435)
- Erik Schleicher (ORCID: https://orcid.org/0000-0003-3010-9528)
- Katherine E Buckton
Institutions
- Carl von Ossietzky Universität Oldenburg (DE)
- University of Freiburg (DE)
- University of Oxford (GB)
Publication Details
- Journal
- Structure
- Published
- 2025-08-28
- DOI
- https://doi.org/10.1016/j.str.2025.08.003
- Citations
- 1
- Primary Topic
- Electromagnetic Fields and Biological Effects
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- Niedersächsisches Ministerium für Wissenschaft und Kultur
- Directorate for Biological Sciences
- U.S. Air Force
- Office of Naval Research
- Army Research Office
- Army Research Laboratory
- Office of Naval Research Global