6z3a: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==== | ==Mec1-Ddc2 (wild-type) in complex with AMP-PNP== | ||
<StructureSection load='6z3a' size='340' side='right'caption='[[6z3a]]' scene=''> | <StructureSection load='6z3a' size='340' side='right'caption='[[6z3a]], [[Resolution|resolution]] 3.80Å' 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'>[[6z3a]] 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=6Z3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z3A 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=6z3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z3a OCA], [https://pdbe.org/6z3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z3a RCSB], [https://www.ebi.ac.uk/pdbsum/6z3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z3a 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]] 3.8Å</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=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=6z3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z3a OCA], [https://pdbe.org/6z3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z3a RCSB], [https://www.ebi.ac.uk/pdbsum/6z3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z3a ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/ATR_YEAST ATR_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 in complex with protein LCD1 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. Phosphorylates LCD1 and RPA2, a subunit of RPA, involved in DNA replication, repair and recombination. Phosphorylates RAD9, CHK1 and RAD53, which leads to the activation of the CHK1 and RAD53 kinases involved in DNA damage repair 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 proteins involved in genome stability. Required for cell growth and meiotic recombination.<ref>PMID:11095737</ref> <ref>PMID:11140636</ref> <ref>PMID:11359899</ref> <ref>PMID:12181334</ref> <ref>PMID:12792653</ref> <ref>PMID:15369670</ref> <ref>PMID:15458641</ref> <ref>PMID:15975089</ref> <ref>PMID:16148046</ref> <ref>PMID:16365046</ref> <ref>PMID:8065923</ref> <ref>PMID:8553072</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 6z3a" 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]] | |||