6jxa
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Tel1 kinase compact monomer== | |
| + | <StructureSection load='6jxa' size='340' side='right'caption='[[6jxa]], [[Resolution|resolution]] 4.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6jxa]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_(strain_atcc_204508_/_s288c) Saccharomyces cerevisiae (strain atcc 204508 / s288c)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JXA FirstGlance]. <br> | ||
| + | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6jxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jxa OCA], [http://pdbe.org/6jxa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jxa RCSB], [http://www.ebi.ac.uk/pdbsum/6jxa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jxa ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ATM_YEAST 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.<ref>PMID:11095737</ref> <ref>PMID:11239397</ref> <ref>PMID:11430828</ref> <ref>PMID:11544181</ref> <ref>PMID:11707419</ref> <ref>PMID:12792653</ref> <ref>PMID:12923051</ref> <ref>PMID:15369670</ref> <ref>PMID:15458641</ref> <ref>PMID:15975089</ref> <ref>PMID:16228207</ref> <ref>PMID:7671310</ref> <ref>PMID:8553072</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:31097817</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6jxa" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Xin, J]] | [[Category: Xin, J]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Responds to dna double-strand break]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 05:51, 3 July 2019
Tel1 kinase compact monomer
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