| Structural highlights
5xf8 is a 7 chain structure with sequence from Baker's yeast. This structure supersedes the now removed PDB entry 5h7i. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 5h7i |
| Gene: | MCM2, YBL023C, YBL0438 (Baker's yeast), MCM3, YEL032W, SYGP-ORF23 (Baker's yeast), MCM4, CDC54, HCD21, YPR019W, YP9531.13 (Baker's yeast), MCM5, CDC46, YLR274W, L9328.1 (Baker's yeast), MCM6, YGL201C (Baker's yeast), MCM7, CDC47, YBR202W, YBR1441 (Baker's yeast), TAH11, CDT1, SID2, YJR046W, J1641 (Baker's yeast) |
| Activity: | DNA helicase, with EC number 3.6.4.12 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[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.[1] [2] [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.[3] [4] [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.[5] [6] [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.[7] [8] [CDT1_YEAST] DNA replication licensing factor, required for pre-replication complex assembly. Faithful duplication of the genetic material requires 'once per cell cycle' DNA replication initiation and elongation. Central to this control is the tightly regulated formation of prereplicative complexes (preRCs) at future origins of DNA replication. Required for the recruitment of the MCM2-7 helicase complex to the replication origins.[9] [10] [11] [12] [13] [14] [15] [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.[16] [17] [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.[18] [19]
Publication Abstract from PubMed
The minichromosome maintenance complex (MCM) hexameric complex (Mcm2-7) forms the core of the eukaryotic replicative helicase. During G1 phase, two Cdt1-Mcm2-7 heptamers are loaded onto each replication origin by the origin-recognition complex (ORC) and Cdc6 to form an inactive MCM double hexamer (DH), but the detailed loading mechanism remains unclear. Here we examine the structures of the yeast MCM hexamer and Cdt1-MCM heptamer from Saccharomyces cerevisiae. Both complexes form left-handed coil structures with a 10-15-A gap between Mcm5 and Mcm2, and a central channel that is occluded by the C-terminal domain winged-helix motif of Mcm5. Cdt1 wraps around the N-terminal regions of Mcm2, Mcm6 and Mcm4 to stabilize the whole complex. The intrinsic coiled structures of the precursors provide insights into the DH formation, and suggest a spring-action model for the MCM during the initial origin melting and the subsequent DNA unwinding.
Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer.,Zhai Y, Cheng E, Wu H, Li N, Yung PY, Gao N, Tye BK Nat Struct Mol Biol. 2017 Mar;24(3):300-308. doi: 10.1038/nsmb.3374. Epub 2017, Feb 13. PMID:28191894[20]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Jacobson MD, Munoz CX, Knox KS, Williams BE, Lu LL, Cross FR, Vallen EA. Mutations in SID2, a novel gene in Saccharomyces cerevisiae, cause synthetic lethality with sic1 deletion and may cause a defect during S phase. Genetics. 2001 Sep;159(1):17-33. PMID:11560884
- ↑ Devault A, Vallen EA, Yuan T, Green S, Bensimon A, Schwob E. Identification of Tah11/Sid2 as the ortholog of the replication licensing factor Cdt1 in Saccharomyces cerevisiae. Curr Biol. 2002 Apr 16;12(8):689-94. PMID:11967159
- ↑ Randell JC, Bowers JL, Rodriguez HK, Bell SP. Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Mol Cell. 2006 Jan 6;21(1):29-39. PMID:16387651 doi:http://dx.doi.org/10.1016/j.molcel.2005.11.023
- ↑ Kawasaki Y, Kim HD, Kojima A, Seki T, Sugino A. Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro. Genes Cells. 2006 Jul;11(7):745-56. PMID:16824194 doi:http://dx.doi.org/10.1111/j.1365-2443.2006.00975.x
- ↑ Asano T, Makise M, Takehara M, Mizushima T. Interaction between ORC and Cdt1p of Saccharomyces cerevisiae. FEMS Yeast Res. 2007 Dec;7(8):1256-62. Epub 2007 Sep 6. PMID:17825064 doi:http://dx.doi.org/10.1111/j.1567-1364.2007.00299.x
- ↑ Chen S, de Vries MA, Bell SP. Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2-7 loading. Genes Dev. 2007 Nov 15;21(22):2897-907. PMID:18006685 doi:http://dx.doi.org/10.1101/gad.1596807
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Zhai Y, Cheng E, Wu H, Li N, Yung PY, Gao N, Tye BK. Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer. Nat Struct Mol Biol. 2017 Mar;24(3):300-308. doi: 10.1038/nsmb.3374. Epub 2017, Feb 13. PMID:28191894 doi:http://dx.doi.org/10.1038/nsmb.3374
|
