Structure of European robin cryptochrome 1 reveals a role in circadian rhythms, not magnetoreception
Cryptochromes (CRYs) play critical roles in regulating diverse physiological functions, including circadian rhythms and neuronal firing in light-dependent or -independent fashions. Structural studies of CRYs have highlighted common features, such as the photolyase homology region (PHR), but they also reveal key differences, particularly in the binding of the flavin adenine dinucleotide (FAD) cofactor, leading to a long-standing debate, namely, whether Type I CRYs can function as FAD-dependent photosensors. This study solves the first crystal structure of a Type II CRY from a migratory songbird, namely, the European robin (<i>Erithacus rubecula</i>) CRY1. Structural, biochemical, and computational analyses of erCRY1 reveal that, unlike light-activated Type I and IV CRYs, Type II CRYs do not bind FAD and employ an open primary pocket for protein-protein interactions. These findings offer new insights into the structural basis of CRY function and suggest that migratory song-bird Type II CRYs function as circadian regulators, not magnetoreceptors.
Authors
- Emil Sjulstok (ORCID: https://orcid.org/0000-0003-2938-7248)
- Carla B. Green (ORCID: https://orcid.org/0000-0002-3947-5156)
- Ilia A. Solov’yov (ORCID: https://orcid.org/0000-0002-8626-145X)
- Fabian Schuhmann (ORCID: https://orcid.org/0000-0002-3768-6494)
- Henrik Mouritsen (ORCID: https://orcid.org/0000-0001-7082-4839)
- Yogarany Chelliah
- Anushka Wickramaratne (ORCID: https://orcid.org/0000-0001-5358-8272)
- Brian D. Zoltowski (ORCID: https://orcid.org/0000-0001-6749-0743)
- Joseph S. Takahashi (ORCID: https://orcid.org/0000-0003-0384-8878)
Institutions
- University of Copenhagen (DK)
- Carl von Ossietzky Universität Oldenburg (DE)
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Southern Methodist University (US)
- Southwestern Medical Center (US)
- National Cancer Institute (US)
- Niels Brock (DK)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- iScience
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1016/j.isci.2025.114015
- Primary Topic
- Light effects on plants
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Energy
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- Lundbeckfonden
- Niedersächsisches Ministerium für Wissenschaft und Kultur
- H. Lundbeck A/S
- National Institutes of Health
- Office of Science
- National Institute of General Medical Sciences
- Office of Research Infrastructure Programs, National Institutes of Health
- Argonne National Laboratory