Flavin reduction activates Drosophila cryptochrome

Anand T. Vaidya, Deniz Top, Craig C. Manahan, Joshua M. Tokuda, Sheng Zhang, Lois Pollack, Michael W. Young, Brian R. Crane

Résultat de recherche: Articleexamen par les pairs

99 Citations (Scopus)

Résumé

Entrainment of circadian rhythms in higher organisms relies on light-sensing proteins that communicate to cellular oscillators composed of delayed transcriptional feedback loops. The principal photoreceptor of the fly circadian clock, Drosophila cryptochrome (dCRY), contains a C-terminal tail (CTT) helix that binds beside a FAD cofactor and is essential for light signaling. Light reduces the dCRY FAD to an anionic semiquinone (ASQ) radical and increases CTT proteolytic susceptibility but does not lead to CTT chemical modification. Additional changes in proteolytic sensitivity and small-angle X-ray scattering define a conformational response of the protein to light that centers at the CTT but also involves regions remote from the flavin center. Reduction of the flavin is kinetically coupled to CTT rearrangement. Chemical reduction to either the ASQ or the fully reduced hydroquinone state produces the same conformational response as does light. The oscillator protein Timeless (TIM) contains a sequence similar to the CTT; the corresponding peptide binds dCRY in light and protects the flavin from oxidation. However, TIM mutants therein still undergo dCRY-mediated degradation. Thus, photoreduction to the ASQ releases the dCRY CTT and promotes binding to at least one region of TIM. Flavin reduction by either light or cellular reductants may be a general mechanism of CRY activation.

Langue d'origineEnglish
Pages (de-à)20455-20460
Nombre de pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Numéro de publication51
DOI
Statut de publicationPublished - déc. 17 2013
Publié à l'externeOui

ASJC Scopus Subject Areas

  • General

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