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'''Unreleased structure'''


The entry 9zd3 is ON HOLD
==Cryo-EM structure of ATR-ATRIP-ETAA1 AAD==
<StructureSection load='9zd3' size='340' side='right'caption='[[9zd3]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9zd3]] 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=9ZD3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ZD3 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]] 3&#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>, <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=9zd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9zd3 OCA], [https://pdbe.org/9zd3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9zd3 RCSB], [https://www.ebi.ac.uk/pdbsum/9zd3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9zd3 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ATR_HUMAN ATR_HUMAN] Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome;Seckel syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/ATR_HUMAN ATR_HUMAN] 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. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication.<ref>PMID:10597277</ref> <ref>PMID:10608806</ref> <ref>PMID:10859164</ref> <ref>PMID:11114888</ref> <ref>PMID:11418864</ref> <ref>PMID:11673449</ref> <ref>PMID:11721054</ref> <ref>PMID:11865061</ref> <ref>PMID:12526805</ref> <ref>PMID:12791985</ref> <ref>PMID:12814551</ref> <ref>PMID:14657349</ref> <ref>PMID:14729973</ref> <ref>PMID:14742437</ref> <ref>PMID:15210935</ref> <ref>PMID:15314022</ref> <ref>PMID:15496423</ref> <ref>PMID:16260606</ref> <ref>PMID:21144835</ref> <ref>PMID:27723717</ref> <ref>PMID:27723720</ref> <ref>PMID:9427750</ref> <ref>PMID:9636169</ref> <ref>PMID:9925639</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.


Authors:  
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>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9zd3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li B]]
[[Category: Pavletich NP]]
Retrieved from "https://proteopedia.org/9zd3"