title: A putative flavin electron transport pathway is differentially utilized in Xenopus CRY1 and CRY2.
abstract: Xenopus laevis cryptochromes (xCRYs) can suppress xCLOCK/xBMAL1-mediated activation of a period E box-containing promoter. This suppression is a crucial part of the vertebrate circadian oscillator. Similar to CRYs in other species, as well as to the closely related photolyases, xCRYs have a conserved flavin binding domain. We show here that an intact flavin binding domain is required for normal function. However, it appears that each xCRY may utilize the bound flavin differently. Mutation in any of the three conserved tryptophan residues in the putative electron transport chain inhibits xCRY2b function, while only the mutation in the last of the three tryptophans significantly affects xCRY1 function. Although knockout studies in mice have suggested that CRY1 and CRY2 are not totally redundant, this is the first time that molecular/biochemical differences between CRY1 and CRY2 have been demonstrated. Both CRYs seem to require an intact flavin binding domain, suggesting that electron transport is important in their ability to suppress CLOCK/BMAL1 activation. However, only xCRY2b appears to depend on electron transport through the conserved tryptophan pathway.
authors.affiliation: NSF Center for Biological Timing, Department of Biology, University of Virginia, Charlottesville, VA 22904, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: C B
authors.initials: CB
authors.lastname: Green
mesh_terms: D000818:Animals; D056931:Cryptochromes; D029721:Drosophila Proteins; D004579:Electron Transport; D005136:Eye Proteins; D005415:Flavins / Q000378:metabolism*; D005420:Flavoproteins / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate; D043562:Receptors, G-Protein-Coupled; D014982:Xenopus laevis
chemical_list: C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005415:Flavins; D005420:Flavoproteins; D043562:Receptors, G-Protein-Coupled; C119828:cry protein, Drosophila