8b4j: Difference between revisions
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==Rfa1-N-terminal domain in complex with phosphorylated Ddc2== | |||
<StructureSection load='8b4j' size='340' side='right'caption='[[8b4j]], [[Resolution|resolution]] 1.58Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8b4j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B4J FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.58Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=8b4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b4j OCA], [https://pdbe.org/8b4j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b4j RCSB], [https://www.ebi.ac.uk/pdbsum/8b4j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b4j ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RFA1_YEAST RFA1_YEAST] Binds to single-stranded sequences participating in DNA replication in addition to those mediating transcriptional repression (URS1) and activation (CAR1). Stimulates the activity of a cognate strand exchange protein (SEP1). It cooperates with T-AG and DNA topoisomerase I to unwind template DNA containing the simian virus 40 origin of DNA replication. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The cell cycle checkpoint kinase Mec1(ATR) and its integral partner Ddc2(ATRIP) are vital for the DNA damage and replication stress response. Mec1-Ddc2 "senses" single-stranded DNA (ssDNA) by being recruited to the ssDNA binding Replication Protein A (RPA) via Ddc2. In this study, we show that a DNA damage-induced phosphorylation circuit modulates checkpoint recruitment and function. We demonstrate that Ddc2-RPA interactions modulate the association between RPA and ssDNA and that Rfa1-phosphorylation aids in the further recruitment of Mec1-Ddc2. We also uncover an underappreciated role for Ddc2 phosphorylation that enhances its recruitment to RPA-ssDNA that is important for the DNA damage checkpoint in yeast. The crystal structure of a phosphorylated Ddc2 peptide in complex with its RPA interaction domain provides molecular details of how checkpoint recruitment is enhanced, which involves Zn(2+). Using electron microscopy and structural modeling approaches, we propose that Mec1-Ddc2 complexes can form higher order assemblies with RPA when Ddc2 is phosphorylated. Together, our results provide insight into Mec1 recruitment and suggest that formation of supramolecular complexes of RPA and Mec1-Ddc2, modulated by phosphorylation, would allow for rapid clustering of damage foci to promote checkpoint signaling. | |||
A DNA damage-induced phosphorylation circuit enhances Mec1(ATR) Ddc2(ATRIP) recruitment to Replication Protein A.,Yates LA, Tannous EA, Morgan RM, Burgers PM, Zhang X Proc Natl Acad Sci U S A. 2023 Apr 4;120(14):e2300150120. doi: , 10.1073/pnas.2300150120. Epub 2023 Mar 30. PMID:36996117<ref>PMID:36996117</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8b4j" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae]] | |||
[[Category: Yates LA]] | |||
[[Category: Zhang X]] | |||
Revision as of 09:53, 27 September 2023
Rfa1-N-terminal domain in complex with phosphorylated Ddc2Rfa1-N-terminal domain in complex with phosphorylated Ddc2
Structural highlights
FunctionRFA1_YEAST Binds to single-stranded sequences participating in DNA replication in addition to those mediating transcriptional repression (URS1) and activation (CAR1). Stimulates the activity of a cognate strand exchange protein (SEP1). It cooperates with T-AG and DNA topoisomerase I to unwind template DNA containing the simian virus 40 origin of DNA replication. Publication Abstract from PubMedThe cell cycle checkpoint kinase Mec1(ATR) and its integral partner Ddc2(ATRIP) are vital for the DNA damage and replication stress response. Mec1-Ddc2 "senses" single-stranded DNA (ssDNA) by being recruited to the ssDNA binding Replication Protein A (RPA) via Ddc2. In this study, we show that a DNA damage-induced phosphorylation circuit modulates checkpoint recruitment and function. We demonstrate that Ddc2-RPA interactions modulate the association between RPA and ssDNA and that Rfa1-phosphorylation aids in the further recruitment of Mec1-Ddc2. We also uncover an underappreciated role for Ddc2 phosphorylation that enhances its recruitment to RPA-ssDNA that is important for the DNA damage checkpoint in yeast. The crystal structure of a phosphorylated Ddc2 peptide in complex with its RPA interaction domain provides molecular details of how checkpoint recruitment is enhanced, which involves Zn(2+). Using electron microscopy and structural modeling approaches, we propose that Mec1-Ddc2 complexes can form higher order assemblies with RPA when Ddc2 is phosphorylated. Together, our results provide insight into Mec1 recruitment and suggest that formation of supramolecular complexes of RPA and Mec1-Ddc2, modulated by phosphorylation, would allow for rapid clustering of damage foci to promote checkpoint signaling. A DNA damage-induced phosphorylation circuit enhances Mec1(ATR) Ddc2(ATRIP) recruitment to Replication Protein A.,Yates LA, Tannous EA, Morgan RM, Burgers PM, Zhang X Proc Natl Acad Sci U S A. 2023 Apr 4;120(14):e2300150120. doi: , 10.1073/pnas.2300150120. Epub 2023 Mar 30. PMID:36996117[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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