View source for 7sic


==Human ATM Dimer==
<StructureSection load='7sic' size='340' side='right'caption='[[7sic]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SIC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.51&#8491;</td></tr>
<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'>[https://proteopedia.org/fgij/fg.htm?mol=7sic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sic OCA], [https://pdbe.org/7sic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sic RCSB], [https://www.ebi.ac.uk/pdbsum/7sic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sic ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
DNA double-strand breaks (DSBs) can lead to mutations, chromosomal rearrangements, genome instability, and cancer. Central to the sensing of DSBs is the ATM (Ataxia-telangiectasia mutated) kinase, which belongs to the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family. In response to DSBs, ATM is activated by the MRN (Mre11-Rad50-Nbs1) protein complex through a poorly-understood process that also requires double-stranded DNA. Previous studies indicate that the FxF/Y motif of Nbs1 directly binds to ATM, and is required to retain active ATM at sites of DNA damage. Here we report the 2.5 A resolution cryo-EM structures of human ATM and its complex with the Nbs1 FxF/Y motif. In keeping with previous structures of ATM and its yeast homolog Tel1, the dimeric human ATM kinase adopts a symmetric, butterfly-shaped structure. The conformation of the ATM kinase domain is most similar to the inactive states of other PIKKs, suggesting that activation may involve an analogous realigning the N and C lobes along with relieving the blockage of the substrate-binding site. We also show that the Nbs1 FxF/Y motif binds to a conserved hydrophobic cleft within the Spiral domain of ATM, suggesting an allosteric mechanism of activation. We evaluate the importance of these structural findings with mutagenesis and biochemical assays.

Structure of the human ATM kinase and mechanism of Nbs1 binding.,Warren C, Pavletich NP Elife. 2022 Jan 25;11. pii: 74218. doi: 10.7554/eLife.74218. PMID:35076389<ref>PMID:35076389</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7sic" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Pavletich NP]]
[[Category: Warren C]]