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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/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). |
| | <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
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).
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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