9th8: Difference between revisions

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New page: '''Unreleased structure''' The entry 9th8 is ON HOLD until sometime in the future Authors: Saleh, A., Noguchi, Y., Schneider, S., Aramayo, R., Speck, C. Description: Cryo-EM structure ...
 
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'''Unreleased structure'''


The entry 9th8 is ON HOLD  until sometime in the future
==Cryo-EM structure of MCM2-7 DH bound to Sld3-Sld7, Cdc45 and DNA==
<StructureSection load='9th8' size='340' side='right'caption='[[9th8]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9th8]] is a 16 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=9TH8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9TH8 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]] 2.9&#8491;</td></tr>
<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=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=9th8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9th8 OCA], [https://pdbe.org/9th8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9th8 RCSB], [https://www.ebi.ac.uk/pdbsum/9th8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9th8 ProSAT]</span></td></tr>
</table>
== Function ==
[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>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Regulated helicase activation by DDK kinase is central for genome stability. However, how DDK phosphorylation primes the MCM2-7 double hexamer (DH) for Sld3-Sld7 binding and Cdc45 loading remained unclear. We define this mechanism through cryo-EM structures of MCM2-7 DH-Sld3-Sld7 (MS) and MCM2-7 DH-Sld3-Sld7-Cdc45 (MSC). We reveal that the autoinhibitory Mcm4 tail engages not only Mcm4 but also Mcm6. Upon DDK-dependent phosphorylation, both of these sites become accessible. In the context of the MS structure, we identify that two short Sld3 motifs that contact Mcm4 and Mcm6 read out the DH phosphorylation state, while the Sld3 Treslin domain (STD) binds to Mcm2. In the MSC structure, Cdc45 dislodges the Sld3 STD from Mcm2, allowing Sld3 to position Cdc45 at the Mcm2/Mcm5 interface. Mutagenesis of the Sld3 STD-Cdc45 interface disrupts Cdc45 loading, validating this interaction. Together, our data reveal a phosphorylation-encoded mechanism coupling DDK-activated Mcm4/Mcm6 surfaces to distal Cdc45 placement, explaining how firing factors choreograph the DH-to-CMG transition.


Authors: Saleh, A., Noguchi, Y., Schneider, S., Aramayo, R., Speck, C.
Structural insights into Sld3-Sld7-dependent Cdc45 loading during replication initiation.,Noguchi Y, Saleh A, Schneider S, Ivanova ME, Chen ZA, Ranjha L, Aramayo R, Tognetti S, Faull SV, Rappsilber J, Speck C Nat Commun. 2026 Aug 14;17(1):9783. doi: 10.1038/s41467-026-76309-6. PMID:42733061<ref>PMID:42733061</ref>


Description: Cryo-EM structure of MCM2-7 DH bound to Sld3-Sld7, Cdc45 and DNA
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Noguchi, Y]]
<div class="pdbe-citations 9th8" style="background-color:#fffaf0;"></div>
[[Category: Aramayo, R]]
== References ==
[[Category: Schneider, S]]
<references/>
[[Category: Speck, C]]
__TOC__
[[Category: Saleh, A]]
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Aramayo R]]
[[Category: Noguchi Y]]
[[Category: Saleh A]]
[[Category: Schneider S]]
[[Category: Speck C]]
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