How the Drosophila Cryptochrome C-terminus mediates magnetosensitivity

Bradlaugh, A. A.; Munro, A. L.; Kattnig, D.; Kurttila, M.; Ikeya, N.; Hoose, A.; Patel, S.; Campesan, S.; Kyriacou, C. P.; Rosato, E.; Woodward, J. R.; Jones, A. R.; Baines, R. A.

doi:10.1101/2025.09.15.676315

bioRxiv · 10.1101/2025.09.15.676315

How the Drosophila Cryptochrome C-terminus mediates magnetosensitivity

Bradlaugh, A. A.·Munro, A. L.·Kattnig, D.·Kurttila, M.·Ikeya, N.·Hoose, A.·Patel, S.·Campesan, S.·Kyriacou, C. P.·Rosato, E.·Woodward, J. R.·Jones, A. R.·Baines, R. A.

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Abstract

The Earths magnetic field plays an important role in the seasonal migrations of many species of animals. A Cryptochrome (CRY)-based radical pair mechanism (RPM) has been suggested to underlie the mechanistic basis of animal magnetosensitivity and navigation. The quantum spin state of a radical pair involving flavin adenine dinucleotide (FAD) bound to CRY in the canonical pocket is sensitive to external magnetic fields that can alter the signalling concentration of activated CRY1-5. However, several experimental observations challenge this model including the finding that the C-terminal fragment of Drosophila CRY (DmCRY), which lacks any canonical FAD binding pocket, and human CRY2, which lacks affinity for FAD, are sufficient to support magnetosensitivity6-9. Here, we use all-atom molecular dynamic (MD) simulations, alongside in vitro and in vivo analyses to reveal that the C-terminus of Drosophila CRY (DmCRY-CT) binds FAD. FAD binding is required for transduction of a magnetic signal within cells, and, in vitro, initiates formation of high molecular weight DmCRY-CT oligomers, including large insoluble aggregates reminiscent of CRY photobodies observed in plants10-14. These results provide a plausible mechanistic basis for several experimental observations that have reported non-canonical magnetosensitivity in animals.

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Bradlaugh, A. A., Munro, A. L., Kattnig, D., Kurttila, M., Ikeya, N., Hoose, A., Patel, S., Campesan, S., Kyriacou, C. P., Rosato, E., Woodward, J. R., Jones, A. R., Baines, R. A.. 2025-09-16. How the Drosophila Cryptochrome C-terminus mediates magnetosensitivity. https://doi.org/10.1101/2025.09.15.676315

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