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| | <StructureSection load='5omb' size='340' side='right'caption='[[5omb]], [[Resolution|resolution]] 1.94Å' scene=''> | | <StructureSection load='5omb' size='340' side='right'caption='[[5omb]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5omb]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OMB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OMB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5omb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Kluyveromyces_lactis_NRRL_Y-1140 Kluyveromyces lactis NRRL Y-1140] and [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=5OMB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OMB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5omb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5omb OCA], [http://pdbe.org/5omb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5omb RCSB], [http://www.ebi.ac.uk/pdbsum/5omb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5omb ProSAT]</span></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=5omb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5omb OCA], [https://pdbe.org/5omb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5omb RCSB], [https://www.ebi.ac.uk/pdbsum/5omb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5omb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. [[http://www.uniprot.org/uniprot/LCD1_KLULA LCD1_KLULA]] Forms a complex with the serine/threonine kinase MEC1 which activates checkpoint signaling upon genotoxic stresses. The MEC1-LCD1 complex is recruited to DNA lesions in order to initiates the DNA repair by homologous recombination. Required for cell growth and meiotic recombination (By similarity). | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Kluyveromyces lactis NRRL Y-1140]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Deshpande, I]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Gasser, S M]] | + | [[Category: Deshpande I]] |
| - | [[Category: Gut, H]] | + | [[Category: Gasser SM]] |
| - | [[Category: Keusch, J J]] | + | [[Category: Gut H]] |
| - | [[Category: Seeber, A]] | + | [[Category: Keusch JJ]] |
| - | [[Category: Shimada, K]] | + | [[Category: Seeber A]] |
| - | [[Category: Coiled-coil domain]]
| + | [[Category: Shimada K]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Oligonucleotide-binding fold]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
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.
Publication Abstract from PubMed
Mec1-Ddc2 (ATR-ATRIP) is a key DNA-damage-sensing kinase that is recruited through the single-stranded (ss) DNA-binding replication protein A (RPA) to initiate the DNA damage checkpoint response. Activation of ATR-ATRIP in the absence of DNA damage is lethal. Therefore, it is important that damage-specific recruitment precedes kinase activation, which is achieved at least in part by Mec1-Ddc2 homodimerization. Here, we report a structural, biochemical, and functional characterization of the yeast Mec1-Ddc2-RPA assembly. High-resolution co-crystal structures of Ddc2-Rfa1 and Ddc2-Rfa1-t11 (K45E mutant) N termini and of the Ddc2 coiled-coil domain (CCD) provide insight into Mec1-Ddc2 homodimerization and damage-site targeting. Based on our structural and functional findings, we present a Mec1-Ddc2-RPA-ssDNA composite structural model. By way of validation, we show that RPA-dependent recruitment of Mec1-Ddc2 is crucial for maintaining its homodimeric state at ssDNA and that Ddc2's recruitment domain and CCD are important for Mec1-dependent survival of UV-light-induced DNA damage.
Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage.,Deshpande I, Seeber A, Shimada K, Keusch JJ, Gut H, Gasser SM Mol Cell. 2017 Oct 19;68(2):431-445.e5. doi: 10.1016/j.molcel.2017.09.019. Epub, 2017 Oct 12. PMID:29033322[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Deshpande I, Seeber A, Shimada K, Keusch JJ, Gut H, Gasser SM. Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage. Mol Cell. 2017 Oct 19;68(2):431-445.e5. doi: 10.1016/j.molcel.2017.09.019. Epub, 2017 Oct 12. PMID:29033322 doi:http://dx.doi.org/10.1016/j.molcel.2017.09.019
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