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.

The Earth's 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 CRY. 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 magnetosensitivity. 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 plants. These results provide a plausible mechanistic basis for several experimental observations that have reported non-canonical magnetosensitivity in animals.