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Published July 17, 2019 | Version v1
Journal article Open

Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions

Creators

  • 1. University of Gothenburg
  • 2. Albert-Ludwigs-Universität Freiburg
  • 3. University of Jyväskylä
  • 4. University of Chicago

Description

Cryptochromes are blue-light photoreceptor proteins, which provide input to circadian clocks. The cryptochrome from Drosophila melanogaster (DmCry) 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 DmCry and the related (6-4) photolyase. DmCry 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 DmCry depends on pH. Mutation of a conserved histidine, important for the biochemical activity of DmCry, 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.

Data availability

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials or are available through figshare (doi: 10.6084/m9.figshare.7628648). Additional data related to this paper may be requested from the authors.

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Additional details

Identifiers

DOI
10.1126/sciadv.aaw1531
Other
oai:uchicago.tind.io:10973

Funding

European Research Council
725642
Deutsche Forschungsgemeinschaft
235777276/GRK1976
Swedish Foundation for International Cooperation in Research and Higher Education
Swedish Foundation for Strategic Research
Academy of Finland
296135
Jane and Aatos Erkko Foundation

UChicago Information

Division(s)
Institutes & Centers
Center(s) or Institute(s)
Center for Advanced Radiation Sources