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Title: Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions

Abstract

Cryptochromes are blue-light photoreceptor proteins, which provide input to circadian clocks. The cryptochrome fromDrosophila 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 inDmCry 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 inDmCry depends on pH. Mutation of a conserved histidine, important for the biochemical activity ofDmCry, 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.

Authors:
ORCiD logo [1]; ORCiD logo [2];  [3]; ORCiD logo [3]; ORCiD logo [3];  [2];  [2];  [4];  [5]; ORCiD logo [5]; ORCiD logo [2]; ORCiD logo [3]
  1. Univ. of Gothenburg (Sweden); Lund Univ. (Sweden)
  2. Albert-Ludwigs-Univ. Freiburg (Germany). Inst. of Physical Chemistry
  3. Univ. of Gothenburg (Sweden)
  4. Univ. of Jyvaskyla (Finland)
  5. Univ. of Chicago, IL (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1545869
Grant/Contract Number:  
[AC02-06CH11357]
Resource Type:
Accepted Manuscript
Journal Name:
Science Advances
Additional Journal Information:
[ Journal Volume: 5; Journal Issue: 7]; Journal ID: ISSN 2375-2548
Publisher:
AAAS
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Berntsson, Oskar, Rodriguez, Ryan, Henry, Léocadie, Panman, Matthijs R., Hughes, Ashley J., Einholz, Christopher, Weber, Stefan, Ihalainen, Janne A., Henning, Robert, Kosheleva, Irina, Schleicher, Erik, and Westenhoff, Sebastian. Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions. United States: N. p., 2019. Web. doi:10.1126/sciadv.aaw1531.
Berntsson, Oskar, Rodriguez, Ryan, Henry, Léocadie, Panman, Matthijs R., Hughes, Ashley J., Einholz, Christopher, Weber, Stefan, Ihalainen, Janne A., Henning, Robert, Kosheleva, Irina, Schleicher, Erik, & Westenhoff, Sebastian. Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions. United States. doi:10.1126/sciadv.aaw1531.
Berntsson, Oskar, Rodriguez, Ryan, Henry, Léocadie, Panman, Matthijs R., Hughes, Ashley J., Einholz, Christopher, Weber, Stefan, Ihalainen, Janne A., Henning, Robert, Kosheleva, Irina, Schleicher, Erik, and Westenhoff, Sebastian. Wed . "Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions". United States. doi:10.1126/sciadv.aaw1531. https://www.osti.gov/servlets/purl/1545869.
@article{osti_1545869,
title = {Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions},
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},
abstractNote = {Cryptochromes are blue-light photoreceptor proteins, which provide input to circadian clocks. The cryptochrome fromDrosophila 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 inDmCry 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 inDmCry depends on pH. Mutation of a conserved histidine, important for the biochemical activity ofDmCry, 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.},
doi = {10.1126/sciadv.aaw1531},
journal = {Science Advances},
number = [7],
volume = [5],
place = {United States},
year = {2019},
month = {7}
}

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