6z2x
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Mec1-Ddc2 (F2244L mutant) in complex with Mg AMP-PNP (State II)== |
| - | <StructureSection load='6z2x' size='340' side='right'caption='[[6z2x]]' scene=''> | + | <StructureSection load='6z2x' size='340' side='right'caption='[[6z2x]], [[Resolution|resolution]] 3.20Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6z2x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z2X FirstGlance]. <br> |
| - | </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=6z2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z2x OCA], [https://pdbe.org/6z2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z2x RCSB], [https://www.ebi.ac.uk/pdbsum/6z2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z2x ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</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>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6z2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z2x OCA], [https://pdbe.org/6z2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z2x RCSB], [https://www.ebi.ac.uk/pdbsum/6z2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z2x ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/LCD1_YEAST LCD1_YEAST] Forms a complex with the serine/threonine kinase MEC1 which activates checkpoint signaling upon genotoxic stresses. The MEC1-LCD1 complex is recruited by the single-strand-binding protein complex RPA to DNA lesions in order to initiate the DNA repair by homologous recombination, after the MRX-complex and TEL1 are displaced. Required for the recruitment of MEC1 to DNA lesions, the activation of CHK1 and RAD53 kinases and phosphorylation of RAD9 in response to DNA damage. Required for cell growth and meiotic recombination.<ref>PMID:10950868</ref> <ref>PMID:11060031</ref> <ref>PMID:11154263</ref> <ref>PMID:11707419</ref> <ref>PMID:11983176</ref> <ref>PMID:12181334</ref> <ref>PMID:15369670</ref> <ref>PMID:16148046</ref> <ref>PMID:16365046</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In response to DNA damage or replication fork stalling, the basal activity of Mec1(ATR) is stimulated in a cell-cycle-dependent manner, leading to cell-cycle arrest and the promotion of DNA repair. Mec1(ATR) dysfunction leads to cell death in yeast and causes chromosome instability and embryonic lethality in mammals. Thus, ATR is a major target for cancer therapies in homologous recombination-deficient cancers. Here we identify a single mutation in Mec1, conserved in ATR, that results in constitutive activity. Using cryo-electron microscopy, we determine the structures of this constitutively active form (Mec1(F2244L)-Ddc2) at 2.8 A and the wild type at 3.8 A, both in complex with Mg(2+)-AMP-PNP. These structures yield a near-complete atomic model for Mec1-Ddc2 and uncover the molecular basis for low basal activity and the conformational changes required for activation. Combined with biochemical and genetic data, we discover key regulatory regions and propose a Mec1 activation mechanism. | ||
| + | |||
| + | Mechanism of auto-inhibition and activation of Mec1(ATR) checkpoint kinase.,Tannous EA, Yates LA, Zhang X, Burgers PM Nat Struct Mol Biol. 2021 Jan;28(1):50-61. doi: 10.1038/s41594-020-00522-0. Epub , 2020 Nov 9. PMID:33169019<ref>PMID:33169019</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6z2x" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Saccharomyces cerevisiae S288C]] |
| + | [[Category: Yates LA]] | ||
| + | [[Category: Zhang X]] | ||
Current revision
Mec1-Ddc2 (F2244L mutant) in complex with Mg AMP-PNP (State II)
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