6jxa | pdb_00006jxa

Tel1 kinase compact monomer

Loading... Status: waiting for Mol* initialization Structural highlights 6jxa is a 1 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ATM_YEAST] Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Recruited by the MRX-complex to sites of DNA lesions immediately after damage to initiate non-homologous end-joining (NHEJ). Subsequently displaced by the RPA complex in a reaction probably involving the SAE2 protein. Phosphorylates MRE11 and XRS2, 2 subunits of the MRX-complex. The phosphorylation of MRE11 is a feedback response from the checkpoint signaling pathway. Phosphorylates RAD9, CHK1 and RAD53, leading to the activation of the CHK1 and RAD23 kinases involved in the DNA damage response cascade. Phosphorylates histone H2A to form H2AS128ph (gamma-H2A) at sites of DNA damage, also involved in the regulation of DNA damage response mechanism. Phosphorylates also SLX4 and RTT107 which are involved in genome stability. Required for the control of telomere length and genome stability. Publication Abstract from PubMed ATM/Tel1 is an apical kinase that orchestrates the multifaceted DNA damage response. Mutations of ATM/Tel1 are associated with ataxia telangiectasia syndrome. Here, we report cryo-EM structures of symmetric dimer (4.1 A) and asymmetric dimer (4.3 A) of Saccharomyces cerevisiae Tel1. In the symmetric state, the side chains in Tel1 C-terminus (residues 1129-2787) are discernible and an atomic model is built. The substrate binding groove is completely embedded in the symmetric dimer by the intramolecular PRD and intermolecular LID domains. Point mutations in these domains sensitize the S. cerevisiae cells to DNA damage agents and hinder Tel1 activation due to reduced binding affinity for its activator Xrs2/Nbs1. In the asymmetric state, one monomer becomes more compact in two ways: the kinase N-lobe moves down and the Spiral of alpha-solenoid moves upwards, which resemble the conformational changes observed in active mTOR. The accessibility of the activation loop correlates with the synergistic conformational disorders in the TRD1-TRD2 linker, FATC and PRD domains, where critical post-translational modifications and activating mutations are coincidently condensed. This study reveals a tunable allosteric network in ATM/Tel1, which is important for substrate recognition, recruitment and efficient phosphorylation. Structural basis of allosteric regulation of Tel1/ATM kinase.,Xin J, Xu Z, Wang X, Tian Y, Zhang Z, Cai G Cell Res. 2019 May 16. pii: 10.1038/s41422-019-0176-1. doi:, 10.1038/s41422-019-0176-1. PMID:31097817 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase 3D structures

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