6PXO

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

6PXO の概要

• エントリーDOI: 10.2210/pdb6pxo/pdb
• 分子名称: Casein kinase I isoform delta (2 entities in total)
• 機能のキーワード: kinase, serine-threonine kinase, circadian clock protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68413.06

構造登録者

Freeberg, A.,Philpott, J.M.,Tripathi, S.M.,Partch, C.L. (登録日: 2019-07-26, 公開日: 2020-02-12, 最終更新日: 2023-10-11)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)