6PXO

Human Casein Kinase 1 delta (anion-free crystallization conditions)

Summary for 6PXO

• Entry DOI: 10.2210/pdb6pxo/pdb
• Descriptor: Casein kinase I isoform delta (2 entities in total)
• Functional Keywords: kinase, serine-threonine kinase, circadian clock protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 68413.06

Authors

Freeberg, A.,Philpott, J.M.,Tripathi, S.M.,Partch, C.L. (deposition date: 2019-07-26, release date: 2020-02-12, Last modification date: 2023-10-11)

Primary citation

Philpott, J.M.,Narasimamurthy, R.,Ricci, C.G.,Freeberg, A.M.,Hunt, S.R.,Yee, L.E.,Pelofsky, R.S.,Tripathi, S.,Virshup, D.M.,Partch, C.L.
Casein kinase 1 dynamics underlie substrate selectivity and the PER2 circadian phosphoswitch.
Elife, 9:-, 2020

PubMed 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 regulate kinase activity. We show that period-altering kinase mutations from humans to differentially modulate this activation loop switch to elicit predictable changes in PER2 stability, providing a foundation to understand and further manipulate CK1 regulation of circadian rhythms.

PubMed: 32043967
DOI: 10.7554/eLife.52343

Experimental method

X-RAY DIFFRACTION (2 Å)