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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]], [[NMR_Ensembles_of_Models | 19 NMR models]]' scene=''> | + | <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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LE8 FirstGlance]. <br> | + | <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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2le8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2le8 OCA], [http://pdbe.org/2le8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2le8 RCSB], [http://www.ebi.ac.uk/pdbsum/2le8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2le8 ProSAT]</span></td></tr> | + | </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'>[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 == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/CDT1_HUMAN CDT1_HUMAN]] Cooperates with CDC6 to promote the loading of the mini-chromosome maintenance complex onto chromatin to form the pre-replication complex necessary to initiate DNA replication. Binds DNA in a sequence-, strand-, and conformation-independent manner. Potential oncogene.<ref>PMID:11125146</ref> <ref>PMID:21856198</ref> <ref>PMID:14672932</ref> <ref>PMID:14993212</ref> [UniProtKB:Q8R4E9] | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Liu, C]] | + | [[Category: Liu C]] |
| - | [[Category: Wei, Z]] | + | [[Category: Wei Z]] |
| - | [[Category: Zhu, G]] | + | [[Category: Zhu G]] |
| - | [[Category: Dna replication]]
| + | |
| - | [[Category: Replication]]
| + | |
| Structural highlights
Function
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.[1]
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ishimi Y. A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex. J Biol Chem. 1997 Sep 26;272(39):24508-13. PMID:9305914
- ↑ Liu C, Wu R, Zhou B, Wang J, Wei Z, Tye BK, Liang C, Zhu G. Structural insights into the Cdt1-mediated MCM2-7 chromatin loading. Nucleic Acids Res. 2012 Apr;40(7):3208-17. doi: 10.1093/nar/gkr1118. Epub 2011, Dec 2. PMID:22140117 doi:http://dx.doi.org/10.1093/nar/gkr1118
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