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Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions

Berntsson, Oskar LU ; Rodriguez, Ryan ; Henry, Léocadie ; Panman, Matthijs R. ; Hughes, Ashley J. ; Einholz, Christopher ; Weber, Stefan ; Ihalainen, Janne A. ; Henning, Robert and Kosheleva, Irina , et al. (2019) In Science Advances 5(7).
Abstract

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... (More)

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.

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publication status
published
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Science Advances
volume
5
issue
7
article number
eaaw1531
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85069837025
  • pmid:31328161
ISSN
2375-2548
DOI
10.1126/sciadv.aaw1531
language
English
LU publication?
yes
id
57ceace5-761d-4710-8f29-681f2341f5e4
date added to LUP
2019-08-29 15:10:59
date last changed
2019-11-29 03:00:25
@article{57ceace5-761d-4710-8f29-681f2341f5e4,
  abstract     = {<p>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.</p>},
  author       = {Berntsson, Oskar and Rodriguez, Ryan and Henry, Léocadie and Panman, Matthijs R. and Hughes, Ashley J. and Einholz, Christopher and Weber, Stefan and Ihalainen, Janne A. and Henning, Robert and Kosheleva, Irina and Schleicher, Erik and Westenhoff, Sebastian},
  issn         = {2375-2548},
  language     = {eng},
  month        = {07},
  number       = {7},
  publisher    = {American Association for the Advancement of Science (AAAS)},
  series       = {Science Advances},
  title        = {Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions},
  url          = {http://dx.doi.org/10.1126/sciadv.aaw1531},
  doi          = {10.1126/sciadv.aaw1531},
  volume       = {5},
  year         = {2019},
}