Circadian Conformational Change of the Neurospora Clock Protein FREQUENCY Triggered by Clustered Hyperphosphorylation of a Basic Domain

FRQ, a clock protein, is phosphorylated at up to 113 sites throughout the day before degradation.

• Two amphipathic motifs in FRQ facilitate long-distance interactions between different regions of the protein.
• These interactions are necessary for the stable association of casein kinase 1a (CK1a) with FRQ.
• CK1a phosphorylates the positively charged N-terminal domain of FRQ at up to 46 nonconsensus sites.
• Phosphorylation may induce a conformational change in FRQ, likely due to electrostatic repulsion.
• The conformational change is associated with the recruitment of FRQ for degradation via the PEST1 signal.

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