7P7F

Crystal structure of phosphorylated pT220 Casein Kinase I delta (CK1d), conformation 1

7P7F の概要

• エントリーDOI: 10.2210/pdb7p7f/pdb
• 分子名称: Casein kinase I isoform delta, SULFATE ION, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: casein kinase, ck1d, csnk1d, conformation plasticity, alpha g, activation segment, phosphorylation., structural genomics, structural genomics consortium, sgc, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 141297.85

構造登録者

Chaikuad, A.,Zhubi, R.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2021-07-19, 公開日: 2022-04-13, 最終更新日: 2024-10-16)

主引用文献

Cullati, S.N.,Chaikuad, A.,Chen, J.S.,Gebel, J.,Tesmer, L.,Zhubi, R.,Navarrete-Perea, J.,Guillen, R.X.,Gygi, S.P.,Hummer, G.,Dotsch, V.,Knapp, S.,Gould, K.L.
Kinase domain autophosphorylation rewires the activity and substrate specificity of CK1 enzymes.
Mol.Cell, 82:2006-, 2022

PubMed Abstract: CK1s are acidophilic serine/threonine kinases with multiple critical cellular functions; their misregulation contributes to cancer, neurodegenerative diseases, and sleep phase disorders. Here, we describe an evolutionarily conserved mechanism of CK1 activity: autophosphorylation of a threonine (T220 in human CK1δ) located at the N terminus of helix αG, proximal to the substrate binding cleft. Crystal structures and molecular dynamics simulations uncovered inherent plasticity in αG that increased upon T220 autophosphorylation. The phosphorylation-induced structural changes significantly altered the conformation of the substrate binding cleft, affecting substrate specificity. In T220 phosphorylated yeast and human CK1s, activity toward many substrates was decreased, but we also identified a high-affinity substrate that was phosphorylated more rapidly, and quantitative phosphoproteomics revealed that disrupting T220 autophosphorylation rewired CK1 signaling in Schizosaccharomyces pombe. T220 is present exclusively in the CK1 family, thus its autophosphorylation may have evolved as a unique regulatory mechanism for this important family.

PubMed: 35353987
DOI: 10.1016/j.molcel.2022.03.005

実験手法

X-RAY DIFFRACTION (1.96 Å)