6RU8

Crystal structure of Casein Kinase I delta (CK1d) in complex with triple phosphorylated p63 PAD3P peptide

6RU8 の概要

• エントリーDOI: 10.2210/pdb6ru8/pdb
• 分子名称: Casein kinase I isoform delta, Tumor protein 63, ADENOSINE-5'-DIPHOSPHATE, ... (7 entities in total)
• 機能のキーワード: ck1 delta, ck1delta, csnk1d, tp63, p63, kinase substrate complex, structural genomics, structural genomics consortium, sgc, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 146343.77

構造登録者

Chaikuad, A.,Tuppi, M.,Gebel, J.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Dotsch, V.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2019-05-27, 公開日: 2020-05-13, 最終更新日: 2024-10-23)

主引用文献

Gebel, J.,Tuppi, M.,Chaikuad, A.,Hotte, K.,Schroder, M.,Schulz, L.,Lohr, F.,Gutfreund, N.,Finke, F.,Henrich, E.,Mezhyrova, J.,Lehnert, R.,Pampaloni, F.,Hummer, G.,Stelzer, E.H.K.,Knapp, S.,Dotsch, V.
p63 uses a switch-like mechanism to set the threshold for induction of apoptosis.
Nat.Chem.Biol., 16:1078-1086, 2020

PubMed Abstract: The p53 homolog TAp63α is the transcriptional key regulator of genome integrity in oocytes. After DNA damage, TAp63α is activated by multistep phosphorylation involving multiple phosphorylation events by the kinase CK1, which triggers the transition from a dimeric and inactive conformation to an open and active tetramer that initiates apoptosis. By measuring activation kinetics in ovaries and single-site phosphorylation kinetics in vitro with peptides and full-length protein, we show that TAp63α phosphorylation follows a biphasic behavior. Although the first two CK1 phosphorylation events are fast, the third one, which constitutes the decisive step to form the active conformation, is slow. Structure determination of CK1 in complex with differently phosphorylated peptides reveals the structural mechanism for the difference in the kinetic behavior based on an unusual CK1/TAp63α substrate interaction in which the product of one phosphorylation step acts as an inhibitor for the following one.

PubMed: 32719556
DOI: 10.1038/s41589-020-0600-3

実験手法

X-RAY DIFFRACTION (1.92 Å)