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Circadian clock activity of cryptochrome relies on tryptophan-mediated photoreduction.


ABSTRACT: 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.

SUBMITTER: Lin C 

PROVIDER: S-EPMC5899454 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Circadian clock activity of cryptochrome relies on tryptophan-mediated photoreduction.

Lin Changfan C   Top Deniz D   Manahan Craig C CC   Young Michael W MW   Crane Brian R BR  

Proceedings of the National Academy of Sciences of the United States of America 20180326 15


Cryptochromes (CRYs) entrain the circadian clocks of plants and animals to light. Irradiation of the <i>Drosophila</i> 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 photoreduct  ...[more]

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