2le8
From Proteopedia
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==The protein complex for DNA replication== | ==The protein complex for DNA replication== | ||
| - | <StructureSection load='2le8' size='340' side='right' caption='[[2le8 | + | <StructureSection load='2le8' size='340' side='right'caption='[[2le8]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2le8]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2le8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LE8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LE8 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2le8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2le8 OCA], [https://pdbe.org/2le8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2le8 RCSB], [https://www.ebi.ac.uk/pdbsum/2le8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2le8 ProSAT]</span></td></tr> |
</table> | </table> | ||
| - | == Disease == | ||
| - | [[http://www.uniprot.org/uniprot/CDT1_HUMAN CDT1_HUMAN]] Defects in CDT1 are the cause of Meier-Gorlin syndrome type 4 (MGORS4) [MIM:[http://omim.org/entry/613804 613804]]. MGORS4 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.<ref>PMID:21358632</ref> <ref>PMID:21358631</ref> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/MCM6_HUMAN MCM6_HUMAN] 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.<ref>PMID:9305914</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Initiation of DNA replication in eukaryotes is exquisitely regulated to ensure that DNA replication occurs exactly once in each cell division. A conserved and essential step for the initiation of eukaryotic DNA replication is the loading of the mini-chromosome maintenance 2-7 (MCM2-7) helicase onto chromatin at replication origins by Cdt1. To elucidate the molecular mechanism of this event, we determined the structure of the human Cdt1-Mcm6 binding domains, the Cdt1(410-440)/MCM6(708-821) complex by NMR. Our structural and site-directed mutagenesis studies showed that charge complementarity is a key determinant for the specific interaction between Cdt1 and Mcm2-7. When this interaction was interrupted by alanine substitutions of the conserved interacting residues, the corresponding yeast Cdt1 and Mcm6 mutants were defective in DNA replication and the chromatin loading of Mcm2, resulting in cell death. Having shown that Cdt1 and Mcm6 interact through their C-termini, and knowing that Cdt1 is tethered to Orc6 during the loading of MCM2-7, our results suggest that the MCM2-7 hexamer is loaded with its C terminal end facing the ORC complex. These results provide a structural basis for the Cdt1-mediated MCM2-7 chromatin loading. | ||
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| + | Structural insights into the Cdt1-mediated MCM2-7 chromatin loading.,Liu C, Wu R, Zhou B, Wang J, Wei Z, Tye BK, Liang C, Zhu G Nucleic Acids Res. 2012 Apr;40(7):3208-17. doi: 10.1093/nar/gkr1118. Epub 2011, Dec 2. PMID:22140117<ref>PMID:22140117</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2le8" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Liu C]] |
| - | [[Category: | + | [[Category: Wei Z]] |
| - | [[Category: | + | [[Category: Zhu G]] |
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Current revision
The protein complex for DNA replication
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Categories: Homo sapiens | Large Structures | Liu C | Wei Z | Zhu G
