6wtb
From Proteopedia
Sort-Tagged Drosophila Cryptochrome
Structural highlights
FunctionCRY1_DROME Blue light-dependent regulator that is the input of the circadian feedback loop. Has no photolyase activity for cyclobutane pyrimidine dimers or 6-4 photoproducts. Regulation of expression by light suggests a role in photoreception for locomotor activity rhythms. Functions, together with per, as a transcriptional repressor required for the oscillation of peripheral circadian clocks and for the correct specification of clock cells. Genes directly activated by the transcription factors Clock (Clk) and cycle (cyc) are repressed by cry. Necessary for light-dependent magnetosensitivity, an intact circadian system is not required for the magnetoreception mechanism to operate. Required for both the naive and trained responses to magnetic field, consistent with the notion that cry is in the input pathway of magnetic sensing.[1] [2] [3] [4] [5] [6] [7] [8] [9] Publication Abstract from PubMedLight-induction of an anionic semiquinone (SQ) flavin radical in Drosophila cryptochrome (dCRY) alters the dCRY conformation to promote binding and degradation of the circadian clock protein Timeless (TIM). Specific peptide ligation with sortase A attaches a nitroxide spin-probe to the dCRY C-terminal tail (CTT) while avoiding deleterious side reactions. Pulse dipolar electron-spin resonance spectroscopy from the CTT nitroxide to the SQ shows that flavin photoreduction shifts the CTT ~1 nm and increases its motion, without causing full displacement from the protein. dCRY engineered to form the neutral SQ serves as a dark-state proxy to reveal that the CTT remains docked when the flavin ring is reduced but uncharged. Substitutions of flavin-proximal His378 promote CTT undocking in the dark or diminish undocking in the light, consistent with molecular dynamics simulations and TIM degradation activity. The His378 variants inform on recognition motifs for dCRY cellular turnover and strategies for developing optogenetic tools. Tuning flavin environment to detect and control light-induced conformational switching in Drosophila cryptochrome.,Chandrasekaran S, Schneps CM, Dunleavy R, Lin C, DeOliveira CC, Ganguly A, Crane BR Commun Biol. 2021 Feb 26;4(1):249. doi: 10.1038/s42003-021-01766-2. PMID:33637846[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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