Casein kinase 1 dynamics underlie substrate selectivity and the PER2 circadian phosphoswitch.

ABSTRACT: Post-translational control of PERIOD stability by Casein Kinase 1δ and ε (CK1) plays a key regulatory role in metazoan circadian rhythms. Despite the deep evolutionary conservation of CK1 in eukaryotes, little is known about its regulation and the factors that influence substrate selectivity on functionally antagonistic sites in PERIOD that directly control circadian period. Here we describe a molecular switch involving a highly conserved anion binding site in CK1. This switch controls conformation of the kinase activation loop and determines which sites on mammalian PER2 are preferentially phosphorylated, thereby directly regulating PER2 stability. Integrated experimental and computational studies shed light on the allosteric linkage between two anion binding sites that dynamically regula

SUBMITTER: Philpott JM 

PROVIDER: S-EPMC7012598 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature