Just-So Stories and Origin Myths: Phosphorylation and Structural Disorder in Circadian Clock Proteins

Abstract

Some longstanding dogmas in the circadian field warrant reexamination in light of recent studies focused on the role of post-translational modifications and intrinsic disorder in core circadian clock proteins of mice and fungi. Such dogmas include the role of turnover in circadian feedback loops and the origin myths describing evolutionary relatedness among circadian clocks. In this Essay, the authors recapitulate recent findings on circadian clock protein regulation by taking an unconventional approach in the form of a dialog between Wizard and Apprentice.

Figure 1. Related Mechanistic Features between Animal and Fungal Clocks

Beginning in the upper left, parts of the heterodimeric TF (oval and circle) interact via PAS domains and bind to the promoters of genes encoding negative elements. The negative-element proteins (yellow and red) have both structured (hexagon and pentagon) and flexible or unstructured regions (clouds). The negative elements form a complex in the nucleus with other proteins (gray background shapes) including CK1 and interact with the TF, causing it to be inactivated. Multisite clock-signaling phosphorylations (P) of the negative elements lead to their inactivation as repressors, and to dissociation, releasing the heterodimeric TF to restart the cycle.