Circadian clock activity of cryptochrome relies on tryptophan-mediated photoreduction

Changfan Lin, Deniz Top, Craig C. Manahan, Michael W. Young, Brian R. Crane

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

60 Citas (Scopus)

Resumen

Cryptochromes (CRYs) entrain the circadian clocks of plants and animals to light. Irradiation of the Drosophila cryptochrome (dCRY) causes reduction of an oxidized flavin cofactor by a chain of conserved tryptophan (Trp) residues. However, it is unclear how redox chemistry within the Trp chain couples to dCRY-mediated signaling. Here, we show that substitutions of four key Trp residues to redox-active tyrosine and redox-inactive phenylalanine tune the light sensitivity of dCRY photoreduction, conformational activation, cellular stability, and targeted degradation of the clock protein timeless (TIM). An essential surface Trp gates electron flow into the flavin cofactor, but can be relocated for enhanced photoactivation. Differential effects of Trp-mediated flavin photoreduction on cellular turnover of TIM and dCRY indicate that these activities are separated in time and space. Overall, the dCRY Trp chain has evolutionary importance for light sensing, and its manipulation has implications for optogenetic applications of CRYs.

Idioma originalEnglish
Páginas (desde-hasta)3822-3827
Número de páginas6
PublicaciónProceedings of the National Academy of Sciences of the United States of America
Volumen115
N.º15
DOI
EstadoPublished - 2018
Publicado de forma externa

Nota bibliográfica

Funding Information:
ACKNOWLEDGMENTS. We thank Jenna Chong for help with protein purification. This work was supported by grants from the NIH: R01GM054339 (to M.W.Y.) and R35GM122535 (to B.R.C.).

Publisher Copyright:
© 2018 National Academy of Sciences. All Rights Reserved.

ASJC Scopus Subject Areas

  • General

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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