7p5z

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Current revision (12:30, 17 July 2024) (edit) (undo)
 
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==Structure of a DNA-loaded MCM double hexamer engaged with the Dbf4-dependent kinase==
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<StructureSection load='7p5z' size='340' side='right'caption='[[7p5z]]' scene=''>
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<StructureSection load='7p5z' size='340' side='right'caption='[[7p5z]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7p5z]] is a 16 chain structure with sequence from [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=7P5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P5Z FirstGlance]. <br>
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</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=7p5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p5z OCA], [https://pdbe.org/7p5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p5z RCSB], [https://www.ebi.ac.uk/pdbsum/7p5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p5z ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7p5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p5z OCA], [https://pdbe.org/7p5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p5z RCSB], [https://www.ebi.ac.uk/pdbsum/7p5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p5z ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MCM2_YEAST MCM2_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity; specifically the MCM2-MCM5 association is proposed to be reversible and to mediate a open ring conformation which may facilitate DNA loading. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Necessary for cell growth.<ref>PMID:19896182</ref> <ref>PMID:19910535</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Loading of the eukaryotic replicative helicase onto replication origins involves two MCM hexamers forming a double hexamer (DH) around duplex DNA. During S phase, helicase activation requires MCM phosphorylation by Dbf4-dependent kinase (DDK), comprising Cdc7 and Dbf4. DDK selectively phosphorylates loaded DHs, but how such fidelity is achieved is unknown. Here, we determine the cryogenic electron microscopy structure of Saccharomyces cerevisiae DDK in the act of phosphorylating a DH. DDK docks onto one MCM ring and phosphorylates the opposed ring. Truncation of the Dbf4 docking domain abrogates DH phosphorylation, yet Cdc7 kinase activity is unaffected. Late origin firing is blocked in response to DNA damage via Dbf4 phosphorylation by the Rad53 checkpoint kinase. DDK phosphorylation by Rad53 impairs DH phosphorylation by blockage of DDK binding to DHs, and also interferes with the Cdc7 active site. Our results explain the structural basis and regulation of the selective phosphorylation of DNA-loaded MCM DHs, which supports bidirectional replication.
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Structural mechanism for the selective phosphorylation of DNA-loaded MCM double hexamers by the Dbf4-dependent kinase.,Greiwe JF, Miller TCR, Locke J, Martino F, Howell S, Schreiber A, Nans A, Diffley JFX, Costa A Nat Struct Mol Biol. 2022 Jan;29(1):10-20. doi: 10.1038/s41594-021-00698-z. Epub , 2021 Dec 28. PMID:34963704<ref>PMID:34963704</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7p5z" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Saccharomyces cerevisiae S288C]]
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[[Category: Costa A]]
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[[Category: Greiwe JF]]
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[[Category: Martino F]]
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[[Category: Miller TCR]]

Current revision

Structure of a DNA-loaded MCM double hexamer engaged with the Dbf4-dependent kinase

PDB ID 7p5z

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