title: Structure of full-length Drosophila cryptochrome.
abstract: The cryptochrome/photolyase (CRY/PL) family of photoreceptors mediates adaptive responses to ultraviolet and blue light exposure in all kingdoms of life. Whereas PLs function predominantly in DNA repair of cyclobutane pyrimidine dimers (CPDs) and 6-4 photolesions caused by ultraviolet radiation, CRYs transduce signals important for growth, development, magnetosensitivity and circadian clocks. Despite these diverse functions, PLs/CRYs preserve a common structural fold, a dependence on flavin adenine dinucleotide (FAD) and an internal photoactivation mechanism. However, members of the CRY/PL family differ in the substrates recognized (protein or DNA), photochemical reactions catalysed and involvement of an antenna cofactor. It is largely unknown how the animal CRYs that regulate circadian rhythms act on their substrates. CRYs contain a variable carboxy-terminal tail that appends the conserved PL homology domain (PHD) and is important for function. Here, we report a 2.3-Å resolution crystal structure of Drosophila CRY with an intact C terminus. The C-terminal helix docks in the analogous groove that binds DNA substrates in PLs. Conserved Trp 536 juts into the CRY catalytic centre to mimic PL recognition of DNA photolesions. The FAD anionic semiquinone found in the crystals assumes a conformation to facilitate restructuring of the tail helix. These results help reconcile the diverse functions of the CRY/PL family by demonstrating how conserved protein architecture and photochemistry can be elaborated into a range of light-driven functions.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Zoltowski
authors.forename: Anand T
authors.initials: AT
authors.lastname: Vaidya
authors.forename: Deniz
authors.initials: D
authors.lastname: Top
authors.forename: Joanne
authors.initials: J
authors.lastname: Widom
authors.forename: Michael W
authors.initials: MW
authors.lastname: Young
authors.forename: Brian R
authors.initials: BR
authors.lastname: Crane
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D057506:Arthropod Antennae; D020134:Catalytic Domain; D056931:Cryptochromes / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D013379:Substrate Specificity; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism
chemical_list: D056931:Cryptochromes; D005182:Flavin-Adenine Dinucleotide; D014364:Tryptophan; D004247:DNA
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