6s8f
From Proteopedia
(Difference between revisions)
| (3 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
==Structure of nucleotide-bound Tel1/ATM== | ==Structure of nucleotide-bound Tel1/ATM== | ||
| - | < | + | <SX load='6s8f' size='340' side='right' viewer='molstar' caption='[[6s8f]], [[Resolution|resolution]] 4.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6s8f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S8F OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6s8f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S8F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S8F FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6s8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s8f OCA], [https://pdbe.org/6s8f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s8f RCSB], [https://www.ebi.ac.uk/pdbsum/6s8f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s8f ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | == Function == | ||
| + | [https://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 == | ||
| + | Yeast Tel1 and its highly conserved human ortholog ataxia-telangiectasia mutated (ATM) are large protein kinases central to the maintenance of genome integrity. Mutations in ATM are found in ataxia-telangiectasia (A-T) patients and ATM is one of the most frequently mutated genes in many cancers. Using cryoelectron microscopy, we present the structure of Tel1 in a nucleotide-bound state. Our structure reveals molecular details of key residues surrounding the nucleotide binding site and provides a structural and molecular basis for its intrinsically low basal activity. We show that the catalytic residues are in a productive conformation for catalysis, but the phosphatidylinositol 3-kinase-related kinase (PIKK) regulatory domain insert restricts peptide substrate access and the N-lobe is in an open conformation, thus explaining the requirement for Tel1 activation. Structural comparisons with other PIKKs suggest a conserved and common allosteric activation mechanism. Our work also provides a structural rationale for many mutations found in A-T and cancer. | ||
| + | |||
| + | Cryo-EM Structure of Nucleotide-Bound Tel1(ATM) Unravels the Molecular Basis of Inhibition and Structural Rationale for Disease-Associated Mutations.,Yates LA, Williams RM, Hailemariam S, Ayala R, Burgers P, Zhang X Structure. 2019 Nov 4. pii: S0969-2126(19)30353-3. doi:, 10.1016/j.str.2019.10.012. PMID:31740029<ref>PMID:31740029</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6s8f" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
| - | </ | + | </SX> |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: | + | [[Category: Ayala R]] |
| - | [[Category: | + | [[Category: Williams RM]] |
| - | [[Category: | + | [[Category: Yates LA]] |
| - | [[Category: | + | [[Category: Zhang X]] |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Structure of nucleotide-bound Tel1/ATM
| |||||||||
