title: Role of structural plasticity in signal transduction by the cryptochrome blue-light photoreceptor.
abstract: Cryptochromes are blue-light photoreceptors that regulate a variety of responses such as growth and circadian rhythms in organisms ranging from bacteria to humans. Cryptochromes share a high level of sequence identity with the light-activated DNA repair enzyme photolyase. Photolyase uses energy from blue light to repair UV-induced photoproducts in DNA through cyclic electron transfer between the catalytic flavin adenine dinucleotide cofactor and the damaged DNA. Cryptochromes lack DNA repair activity, and their mechanism of signal transduction is not known. It is hypothesized that a light-dependent signaling state in cryptochromes is created as a result of an intramolecular redox reaction, resulting in conformational rearrangement and effector binding. Plant and animal cryptochromes possess 30-250 amino acid carboxy-terminal extensions beyond the photolyase-homology region that have been shown to mediate phototransduction. We analyzed the structures of C-terminal domains from an animal and a plant cryptochrome by computational, biophysical, and biochemical methods and found these domains to be intrinsically unstructured. We show that the photolyase-homology region interacts with the C-terminal domain, inducing stable tertiary structure in the C-terminal domain. Importantly, we demonstrate a light-dependent conformational change in the C-terminal domain of Arabidopsis Cry1. Collectively, these findings provide the first biochemical evidence for the proposed conformational rearrangement of cryptochromes upon light exposure.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Partch
authors.forename: Michael W
authors.initials: MW
authors.lastname: Clarkson
authors.forename: Sezgin
authors.initials: S
authors.lastname: Ozgür
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lee
authors.forename: Aziz
authors.initials: A
authors.lastname: Sancar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D029681:Arabidopsis Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D002942:Circular Dichroism; D019295:Computational Biology / Q000379:methods; D056931:Cryptochromes; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D005420:Flavoproteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D008027:Light; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D020419:Photoreceptor Cells, Vertebrate / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000737:chemistry
chemical_list: D029681:Arabidopsis Proteins; C538963:CRY1 protein, human; D056931:Cryptochromes; D029721:Drosophila Proteins; D005420:Flavoproteins; D010446:Peptide Fragments; D014357:Trypsin; D004255:Deoxyribodipyrimidine Photo-Lyase