Photoactivation of <i>Drosophila melanogaster</i> cryptochrome through sequential conformational transitions.

Abstract

Cryptochromes are blue-light photoreceptor proteins, which provide input to circadian clocks. The cryptochrome from <i>Drosophila melanogaster</i> (<i>Dm</i>Cry) modulates the degradation of Timeless and itself. It is unclear how light absorption by the chromophore and the subsequent redox reactions trigger these events. Here, we use nano- to millisecond time-resolved x-ray solution scattering to reveal the light-activated conformational changes in <i>Dm</i>Cry and the related (6-4) photolyase. <i>Dm</i>Cry undergoes a series of structural changes, culminating in the release of the carboxyl-terminal tail (CTT). The photolyase has a simpler structural response. We find that the CTT release in <i>Dm</i>Cry depends on pH. Mutation of a conserved histidine, important for the biochemical activity of <i>Dm</i>Cry, does not affect transduction of the structural signal to the CTT. Instead, molecular dynamics simulations suggest that it stabilizes the CTT in the resting-state conformation. Our structural photocycle unravels the first molecular events of signal transduction in an animal cryptochrome.