2JQL

NMR structure of the yeast Dun1 FHA domain in complex with a doubly phosphorylated (pT) peptide derived from Rad53 SCD1

2JQL の概要

• エントリーDOI: 10.2210/pdb2jql/pdb
• 関連するPDBエントリー: 2JQI 2JQJ
• 分子名称: DNA damage response protein kinase DUN1, Serine/threonine-protein kinase RAD53 (2 entities in total)
• 機能のキーワード: protein/phosphopeptide, cell cycle
• 由来する生物種: Saccharomyces cerevisiae (yeast)
• 細胞内の位置: Nucleus: P39009 P22216
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18671.62

構造登録者

Yuan, C.,Lee, H.,Chang, C.,Heierhorst, J.,Tsai, M. (登録日: 2007-06-02, 公開日: 2008-06-24, 最終更新日: 2024-11-06)

主引用文献

Lee, H.,Yuan, C.,Hammet, A.,Mahajan, A.,Chen, E.S.,Wu, M.R.,Su, M.I.,Heierhorst, J.,Tsai, M.D.
Diphosphothreonine-specific interaction between an SQ/TQ cluster and an FHA domain in the Rad53-Dun1 kinase cascade.
Mol.Cell, 30:767-778, 2008

PubMed Abstract: Forkhead-associated (FHA) domains recognize phosphothreonines, and SQ/TQ cluster domains (SCDs) contain concentrated phosphorylation sites for ATM/ATR-like DNA-damage-response kinases. The Rad53-SCD1 has dual functions in regulating the activation of the Rad53-Dun1 checkpoint kinase cascade but with unknown molecular mechanisms. Here we present structural, biochemical, and genetic evidence that Dun1-FHA possesses an unprecedented diphosphothreonine-binding specificity. The Dun1-FHA has >100-fold increased affinity for diphosphorylated relative to monophosphorylated Rad53-SCD1 due to the presence of two separate phosphothreonine-binding pockets. In vivo, any single threonine of Rad53-SCD1 is sufficient for Rad53 activation and RAD53-dependent survival of DNA damage, but two adjacent phosphothreonines in the Rad53-SCD1 and two phosphothreonine-binding sites in the Dun1-FHA are necessary for Dun1 activation and DUN1-dependent transcriptional responses to DNA damage. The results uncover a phospho-counting mechanism that regulates the specificity of SCD, and provide mechanistic insight into a role of multisite phosphorylation in DNA-damage signaling.

PubMed: 18570878
DOI: 10.1016/j.molcel.2008.05.013

実験手法

SOLUTION NMR