How the Drosophila Cryptochrome C-terminus mediates magnetosensitivity

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.