Vertebrate Cryptochromes are Vestigial Flavoproteins.
All cryptochromes are currently classified as flavoproteins. In animals their best-described role is as components of the circadian clock. This circadian function is variable, and can be either light-dependent or -independent; the molecular origin of this difference is unknown. Type I animal cryptochromes are photoreceptors that entrain an organism's clock to its environment, whereas Type II (including mammals) regulate circadian timing in a light-independent manner. Here, we reveal that, in contrast to Type I, Type II animal cryptochromes lack the structural features to securely bind the photoactive flavin cofactor. We provide a molecular basis for the distinct circadian roles of different animal cryptochromes, which also has significant implications for the putative role of Type II cryptochromes in animal photomagnetoreception.
Manchester Institute of Biotechnology (MIB) and School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.|Photon Science Institute and School of Chemistry, The University of Manchester, Alan Turing Building, Oxford Road, Manchester, M13 9PL, UK.
Roger J
RJ
Kutta
Manchester Institute of Biotechnology (MIB) and School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Nataliya
N
Archipowa
Manchester Institute of Biotechnology (MIB) and School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Linus O
LO
Johannissen
Manchester Institute of Biotechnology (MIB) and School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.|Photon Science Institute and School of Chemistry, The University of Manchester, Alan Turing Building, Oxford Road, Manchester, M13 9PL, UK.
Alex R
AR
Jones
Manchester Institute of Biotechnology (MIB) and School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Nigel S
NS
Scrutton
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002942:Circular Dichroism; D056931:Cryptochromes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry / Q000378:metabolism; D005420:Flavoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010786:Photoreceptor Cells / Q000378:metabolism; D011485:Protein Binding; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; D056931:Cryptochromes; D005420:Flavoproteins; D005182:Flavin-Adenine Dinucleotide