13de: Difference between revisions
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The | ==Cryo-EM structure of ATR-ATRIP-ETAA1 AAD (S95D/S111D)== | ||
<StructureSection load='13de' size='340' side='right'caption='[[13de]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[13de]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=13DE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=13DE 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]] 2.9Å</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=13de FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=13de OCA], [https://pdbe.org/13de PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=13de RCSB], [https://www.ebi.ac.uk/pdbsum/13de PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=13de ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ETAA1_HUMAN ETAA1_HUMAN] Replication stress response protein that accumulates at DNA damage sites and promotes replication fork progression and integrity (PubMed:27601467, PubMed:27723717, PubMed:27723720). Recruited to stalled replication forks via interaction with the RPA complex and directly stimulates ATR kinase activity independently of TOPBP1 (PubMed:27723717, PubMed:27723720, PubMed:30139873). Probably only regulates a subset of ATR targets (PubMed:27723717, PubMed:27723720).<ref>PMID:27601467</ref> <ref>PMID:27723717</ref> <ref>PMID:27723720</ref> <ref>PMID:30139873</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The ATR protein kinase preserves genomic integrity during DNA replication by controlling checkpoints needed for the orderly progression of S phase and for the responses to replication stress. ATR, with its obligate partner ATRIP, is activated by the TOPBP1 and ETAA1 proteins, which control different branches of ATR signaling. TOPBP1 is essential for induction of the S phase checkpoint in response to stalled replication forks, while ETAA1 is required for timely progression to mitosis from an unperturbed S phase. TOPBP1 and ETAA1 contain ATR-activating domains (AADs) of limited homology, but how they activate ATR has not yet been fully elucidated. Here we present the 3.0-A cryo-EM structure of the human ATR-ATRIP complex bound to the TOPBP1 AAD, showing that TOPBP1 activates ATR by inducing a global conformational change that allosterically realigns active site residues in the kinase domain ~70 A away. We also present the 3.3-A structure of the ATR-ATRIP-ETAA1 AAD complex, which reveals a binding mode distinct from TOPBP1. Our data suggest that the distinct binding modes of TOPBP1 and ETAA1 contribute to the different cellular contexts and outcomes of ATR-ATRIP activation. | |||
Structural mechanism of TOPBP1 activating the ATR-ATRIP replication checkpoint kinase.,Li B, Yaseen A, Pavletich NP Nat Struct Mol Biol. 2026 Jul 23. doi: 10.1038/s41594-026-01844-1. PMID:42493622<ref>PMID:42493622</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 13de" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Li B]] | |||
[[Category: Pavletich NP]] | |||
Latest revision as of 06:53, 5 August 2026
Cryo-EM structure of ATR-ATRIP-ETAA1 AAD (S95D/S111D)
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