Takahashi, J. S. Transcriptional architecture of the mammalian circadian clock. Nat. Rev. Genet. 18, 164–179 (2017).
Crane, B. R. & Young, M. W. Interactive features of proteins composing eukaryotic circadian clocks. Ann. Rev. Biochem. 83, 191–219 (2014).
Foley, L. E. & Emery, P. Drosophila cryptochrome: variations in blue. J. Biol. Rhythms 35, 16–27 (2020).
Top, D., Harms, E., Syed, S., Adams, E. L. & Saez, L. GSK-3 and CK2 kinases converge on Timeless to regulate the master clock. Cell Rep. 16, 357–367 (2016).
Jang, A. R., Moravcevic, K., Saez, L., Young, M. W. & Sehgal, A. Drosophila TIM binds Importin α1, and acts as an adapter to transport PER to the nucleus. PLOS Genet. 11 e004974 (2015).
Tauber, E. et al. Natural selection favors a newly derived timeless allele in Drosophila melanogaster. Science 316, 1895–1898 (2007).
Deppisch, P. et al. Adaptation of Drosophila melanogaster to long photoperiods of high-latitude summers is facilitated by the ls-timeless allele. J. Biol. Rhythms 37, 185–201 (2022).
Lin, F. J., Song, W., Meyer-Bernstein, E., Naidoo, N. & Sehgal, A. Photic signaling by cryptochrome in the Drosophila circadian system. Mol. Cell. Biol. 21, 7287–7294 (2001).
Chaves, I. et al. The cryptochromes: blue light photoreceptors in plants and animals. Annu. Rev. Plant Biol. 62, 335–364 (2011).
Ozturk, N. Phylogenetic and functional classification of the photolyase/cryptochrome family. Photochem. Photobiol. 93, 104–111 (2017).
Parico, G. C. G. et al. The human CRY1 tail controls circadian timing by regulating its association with CLOCK:BMAL1. Proc. Natl Acad. Sci. USA 117, 27971–27979 (2020).
Berndt, A. et al. A novel photoreaction mechanism for the circadian blue light photoreceptor Drosophila cryptochrome. J. Biol. Chem. 282, 13011–13021 (2007).
Vaidya, A. T. et al. Flavin reduction activates Drosophila cryptochrome. Proc. Natl Acad. Sci. USA 110, 20455–20460 (2013).
Ozturk, N., Selby, C. P., Annayev, Y., Zhong, D. & Sancar, A. Reaction mechanism of Drosophila cryptochrome. Proc. Natl Acad. Sci. USA 108, 516–521 (2011).
Lin, C. F., Top, D., Manahan, C. C., Young, M. W. & Crane, B. R. Circadian clock activity of cryptochrome relies on tryptophan-mediated photoreduction. Proc. Natl Acad. Sci. USA 115, 3822–3827 (2018).
Lin, C., Schneps, C. M., Chandrasekaran, S., Ganguly, A. & Crane, B. R. Mechanistic insight into light-dependent recognition of Timeless by Drosophila Cryptochrome. Structure 30, 851–861 (2022).
Chandrasekaran, S. et al. Tuning flavin environment to detect and control light-induced conformational switching in Drosophila cryptochrome. Commun. Biol. 4, 249 (2021).
Ganguly, A. et al. Changes in active site histidine hydrogen bonding trigger cryptochrome activation. Proc. Natl Acad. Sci. USA 113, 10073–10078 (2016).
Koh, K., Zheng, X. Z. & Sehgal, A. JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS. Science 312, 1809–1812 (2006).
Peschel, N., Chen, K. F., Szabo, G. & Stanewsky, R. Light-dependent interactions between the Drosophila circadian clock factors Cryptochrome, Jetlag, and Timeless. Curr. Biol. 19, 241–247 (2009).
Yu, D. et al. Optogenetic activation of intracellular antibodies for direct modulation of endogenous proteins. Nat. Methods 16, 1095–1100 (2019).
Gil, A. A. et al. Optogenetic control of protein binding using light-switchable nanobodies. Nat. Commun. 11, 4044 (2020).
Busza, A., Emery-Le, M., Rosbash, M. & Emery, P. Roles of the two Drosophila CRYPTOCHROME structural domains in circadian photoreception. Science 304, 1503–1506 (2004).
Dissel, S. et al. A constitutively active cryptochrome in Drosophila melanogaster. Nat. Neurosci. 7, 834–840 (2004).
Hemsley, M. J. et al. Linear motifs in the C-terminus of D-melanogaster cryptochrome. Biochem. Biophys. Res. Commun. 355, 531–537 (2007).
Vodovar, N., Clayton, J. D., Costa, R., Odell, M. & Kyriacou, C. P. The Drosophila clock protein Timeless is a member of the Arm/HEAT family. Curr. Biol. 12, R610–R611 (2002).
Holzer, S. et al. Crystal structure of the N-terminal domain of human Timeless and its interaction with Tipin. Nucleic Acids Res. 45, 5555–5563 (2017).
Zoltowski, B. D. et al. Structure of full-length Drosophila cryptochrome. Nature 480, 396–399 (2011).
Levy, C. et al. Updated structure of Drosophila cryptochrome. Nature 495, E3–E4 (2013).
Czarna, A. et al. Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function. Cell 153, 1394–1405 (2013).
Sandrelli, F. et al. A molecular basis for natural selection at the timeless locus in Drosophila melanogaster. Science 316, 1898–1900 (2007).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
Kurien, P. et al. TIMELESS mutation alters phase responsiveness and causes advanced sleep phase. Proc. Natl Acad. Sci. USA 116, 12045–12053 (2019).
Schmalen, I. et al. Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc binding and disulfide bond formation. Cell 157, 1203–1215 (2014).
Fribourgh, J. L. et al. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. Elife 9, e55275 (2020).
Nangle, S. N. et al. Molecular assembly of the Period-Cryptochrome circadian transcriptional repressor complex. Elife 3, e03674 (2014).
Engelen, E. et al. Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock. PLoS ONE 8, e56623 (2013).
Baretic, D. et al. Cryo-EM structure of the fork protection complex bound to CMG at a replication fork. Mol. Cell 78, 926–940 (2020).
Xie, S. et al. Timeless interacts with PARP-1 to promote homologous recombination repair. Mol. Cell 60, 163–176 (2015).
Stanewsky, R. et al. The cry(b) mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell 95, 681–692 (1998).
Wang, Y. J., Veglia, G., Zhong, D. P. & Gao, J. L. Activation mechanism of Drosophila cryptochrome through an allosteric switch. Sci. Adv. 7, eabg3815 (2021).
Berntsson, O. et al. Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions. Sci. Adv. 5, eaaw1531 (2019).
Glas, A. F., Schneider, S., Maul, M. J., Hennecke, U. & Carell, T. Crystal structure of the T(6-4)C lesion in complex with a (6-4) DNA photolyase and repair of UV-induced (6-4) and Dewar photolesions. Chemistry 15, 10387–10396 (2009).
Nangle, S., Xing, W. M. & Zheng, N. Crystal structure of mammalian cryptochrome in complex with a small molecule competitor of its ubiquitin ligase. Cell Res. 23, 1417–1419 (2013).
Rosensweig, C. et al. An evolutionary hotspot defines functional differences between CRYPTOCHROMES. Nat. Commun. 9, 1138 (2018).
Tewari, R., Bailes, E., Bunting, K. A. & Coates, J. C. Armadillo-repeat protein functions: questions for little creatures. Trends Cell Biol. 20, 470–481 (2010).
Choi, H. J. et al. A conserved phosphorylation switch controls the interaction between cadherin and β-catenin in vitro and in vivo. Dev. Cell 33, 82–93 (2015).
Goldfarb, D. S., Corbett, A. H., Mason, D. A., Harreman, M. T. & Adam, S. A. Importin α: a multipurpose nuclear-transport receptor. Trends Cell Biol. 14, 505–514 (2004).
Catimel, B. et al. Biophysical characterization of interactions involving importin-α during nuclear import. J. Biol. Chem. 276, 34189–34198 (2001).
Harreman, M. T., Hodel, M. R., Fanara, P., Hodel, A. E. & Corbett, A. H. The auto-inhibitory function of importin α is essential in vivo. J. Biol. Chem. 278, 5854–5863 (2003).
Muok, A. R. et al. Engineered chemotaxis core signaling units indicate a constrained kinase-off state. Sci. Signal. 13, eabc1328 (2020).
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
Bepler, T. et al. Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs. Nat. Methods 16, 1153–1160 (2019).
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
Croll, T. I. ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps. Acta Crystallogr. D 74, 519–530 (2018).
Morin, A. et al. Collaboration gets the most out of software. Elife 2, e01456 (2013).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).
Liebschner, D. et al. Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr. D 75, 861–877 (2019).
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12–21 (2010).
Pintilie, G. et al. Measurement of atom resolvability in cryo-EM maps with Q-scores. Nat. Methods 17, 328–334 (2020).
Kallberg, M. et al. Template-based protein structure modeling using the RaptorX web server. Nat. Protoc. 7, 1511–1522 (2012).
Holm, L. & Laakso, L. M. Dali server update. Nucleic Acids Res. 44, W351–W355 (2016).
More News
Editorial Expression of Concern: Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase – Nature
Quantum control of a cat qubit with bit-flip times exceeding ten seconds – Nature
Venus water loss is dominated by HCO+ dissociative recombination – Nature