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| | <SX load='6hv9' size='340' side='right' viewer='molstar' caption='[[6hv9]], [[Resolution|resolution]] 4.98Å' scene=''> | | <SX load='6hv9' size='340' side='right' viewer='molstar' caption='[[6hv9]], [[Resolution|resolution]] 4.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6hv9]] is a 16 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HV9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6HV9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6hv9]] is a 10 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=6HV9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HV9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.98Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</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'>[http://proteopedia.org/fgij/fg.htm?mol=6hv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hv9 OCA], [http://pdbe.org/6hv9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hv9 RCSB], [http://www.ebi.ac.uk/pdbsum/6hv9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hv9 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=6hv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hv9 OCA], [https://pdbe.org/6hv9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hv9 RCSB], [https://www.ebi.ac.uk/pdbsum/6hv9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hv9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MCM7_YEAST MCM7_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. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity.<ref>PMID:19896182</ref> <ref>PMID:19910535</ref> [[http://www.uniprot.org/uniprot/CDC45_YEAST CDC45_YEAST]] Required for initiation of chromosomal DNA replication. Acts at the origin of replication. Also has a role in minichromosome maintenance.<ref>PMID:8901577</ref> <ref>PMID:9001208</ref> [[http://www.uniprot.org/uniprot/MCM5_YEAST MCM5_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.<ref>PMID:19896182</ref> <ref>PMID:19910535</ref> [[http://www.uniprot.org/uniprot/PSF1_YEAST PSF1_YEAST]] Required for DNA replication. Functions as part of the GINS complex which plays an essential role in the initiation of DNA replication by binding to DNA replication origins and facilitating the assembly of the DNA replication machinery. Required for the chromatin binding of CDC45.<ref>PMID:12730134</ref> [[http://www.uniprot.org/uniprot/PSF3_YEAST PSF3_YEAST]] Functions as part of the GINS complex which plays an essential role in the initiation of DNA replication by binding to DNA replication origins and facilitating the assembly of the DNA replication machinery.[UniProtKB:P40359]<ref>PMID:12730134</ref> [[http://www.uniprot.org/uniprot/MCM4_YEAST MCM4_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. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Required for S phase execution.<ref>PMID:19896182</ref> <ref>PMID:19910535</ref> [[http://www.uniprot.org/uniprot/DPB2_YEAST DPB2_YEAST]] DNA polymerase epsilon (DNA polymerase II) participates in chromosomal DNA replication. It is required during synthesis of the leading and lagging DNA strands at the replication fork and binds at/or near replication origins and moves along DNA with the replication fork. It has 3'-5' proofreading exonuclease activity that correct errors arising during DNA replication. It is also involved in DNA synthesis during DNA repair.<ref>PMID:12124389</ref> [[http://www.uniprot.org/uniprot/PSF2_YEAST PSF2_YEAST]] Functions as part of the GINS complex which plays an essential role in the initiation of DNA replication by binding to DNA replication origins and facilitating the assembly of the DNA replication machinery.<ref>PMID:12730134</ref> [[http://www.uniprot.org/uniprot/MCM6_YEAST MCM6_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. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Required for the entry in S phase and for cell division.<ref>PMID:19896182</ref> <ref>PMID:19910535</ref> [[http://www.uniprot.org/uniprot/MCM3_YEAST MCM3_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. 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> [[http://www.uniprot.org/uniprot/SLD5_YEAST SLD5_YEAST]] Required for DNA replication. Functions as part of the GINS complex which plays an essential role in the initiation of DNA replication by binding to DNA replication origins and facilitating the assembly of the DNA replication machinery.<ref>PMID:12730134</ref> [UniProtKB:P40359] [[http://www.uniprot.org/uniprot/DPOE_YEAST DPOE_YEAST]] DNA polymerase epsilon (DNA polymerase II) participates in chromosomal DNA replication. It is required during synthesis of the leading and lagging DNA strands at the replication fork and binds at/or near replication origins and moves along DNA with the replication fork. It has 3'-5' proofreading exonuclease activity that correct errors arising during DNA replication. It is also involved in DNA synthesis during DNA repair.<ref>PMID:12124389</ref> [[http://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> | + | [https://www.uniprot.org/uniprot/MCM3_YEAST MCM3_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. 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: DNA helicase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ali, F Abid]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Cheung, A]] | + | [[Category: Abid Ali F]] |
| - | [[Category: Costa, A]] | + | [[Category: Cheung A]] |
| - | [[Category: Purkiss, A G]] | + | [[Category: Costa A]] |
| - | [[Category: Aaa+ protein]] | + | [[Category: Purkiss AG]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Dna replication]]
| + | |
| - | [[Category: Helicase]]
| + | |
| - | [[Category: Polymerase]]
| + | |
| Structural highlights
Function
MCM3_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. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Necessary for cell growth.[1] [2]
Publication Abstract from PubMed
Eukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase. A key step is the recruitment of GINS that requires the leading-strand polymerase Pol epsilon, composed of Pol2, Dpb2, Dpb3, Dpb4. While a truncation of the catalytic N-terminal Pol2 supports cell division, Dpb2 and C-terminal Pol2 (C-Pol2) are essential for viability. Dpb2 and C-Pol2 are non-catalytic modules, shown or predicted to be related to an exonuclease and DNA polymerase, respectively. Here, we present the cryo-EM structure of the isolated C-Pol2/Dpb2 heterodimer, revealing that C-Pol2 contains a DNA polymerase fold. We also present the structure of CMG/C-Pol2/Dpb2 on a DNA fork, and find that polymerase binding changes both the helicase structure and fork-junction engagement. Inter-subunit contacts that keep the helicase-polymerase complex together explain several cellular phenotypes. At least some of these contacts are preserved during Pol epsilon-dependent CMG assembly on path to origin firing, as observed with DNA replication reconstituted in vitro.
Structure of DNA-CMG-Pol epsilon elucidates the roles of the non-catalytic polymerase modules in the eukaryotic replisome.,Goswami P, Abid Ali F, Douglas ME, Locke J, Purkiss A, Janska A, Eickhoff P, Early A, Nans A, Cheung AMC, Diffley JFX, Costa A Nat Commun. 2018 Nov 29;9(1):5061. doi: 10.1038/s41467-018-07417-1. PMID:30498216[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009 Nov 13;139(4):719-30. doi: 10.1016/j.cell.2009.10.015. Epub 2009 Nov, 5. PMID:19896182 doi:http://dx.doi.org/10.1016/j.cell.2009.10.015
- ↑ Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi:, 10.1073/pnas.0911500106. Epub 2009 Nov 12. PMID:19910535 doi:http://dx.doi.org/10.1073/pnas.0911500106
- ↑ Goswami P, Abid Ali F, Douglas ME, Locke J, Purkiss A, Janska A, Eickhoff P, Early A, Nans A, Cheung AMC, Diffley JFX, Costa A. Structure of DNA-CMG-Pol epsilon elucidates the roles of the non-catalytic polymerase modules in the eukaryotic replisome. Nat Commun. 2018 Nov 29;9(1):5061. doi: 10.1038/s41467-018-07417-1. PMID:30498216 doi:http://dx.doi.org/10.1038/s41467-018-07417-1
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