Chandler, S.A., Gehrckens, A.S., Shah, L.M.N., Buckton, K.E., Cao, G., Sen, N., Zollitsch, T., Rodriguez, R., Solov'yov, I.A., Schleicher, E., Weber, S., Hore, P.J., Timmel, C.R., Mackenzie, S.R., Benesch, J.L.P. (2025). Light-induced conformational switching and magnetic sensitivity of Drosophila cryptochrome.  Structure 33(11): 1930--1943.e4.

FBrf0263826

Research paper

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.