2JQL
NMR structure of the yeast Dun1 FHA domain in complex with a doubly phosphorylated (pT) peptide derived from Rad53 SCD1
Summary for 2JQL
| Entry DOI | 10.2210/pdb2jql/pdb |
| Related | 2JQI 2JQJ |
| Descriptor | DNA damage response protein kinase DUN1, Serine/threonine-protein kinase RAD53 (2 entities in total) |
| Functional Keywords | protein/phosphopeptide, cell cycle |
| Biological source | Saccharomyces cerevisiae (yeast) |
| Cellular location | Nucleus: P39009 P22216 |
| Total number of polymer chains | 2 |
| Total formula weight | 18671.62 |
| Authors | Yuan, C.,Lee, H.,Chang, C.,Heierhorst, J.,Tsai, M. (deposition date: 2007-06-02, release date: 2008-06-24, Last modification date: 2024-11-06) |
| Primary citation | 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 Cited by 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: 18570878DOI: 10.1016/j.molcel.2008.05.013 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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