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| | ==Crystal structure of Cdt1/geminin complex== | | ==Crystal structure of Cdt1/geminin complex== |
| - | <StructureSection load='2zxx' size='340' side='right' caption='[[2zxx]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='2zxx' size='340' side='right'caption='[[2zxx]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zxx]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1wlq 1wlq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZXX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zxx]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1wlq 1wlq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZXX FirstGlance]. <br> |
| | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">geminin, Gmnn ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Cdt1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">geminin, Gmnn ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Cdt1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2zxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zxx OCA], [http://pdbe.org/2zxx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zxx RCSB], [http://www.ebi.ac.uk/pdbsum/2zxx PDBsum]</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=2zxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zxx OCA], [https://pdbe.org/2zxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zxx RCSB], [https://www.ebi.ac.uk/pdbsum/2zxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zxx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GEMI_MOUSE GEMI_MOUSE]] Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle.<ref>PMID:9635433</ref> <ref>PMID:12192004</ref> Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (By similarity).<ref>PMID:9635433</ref> <ref>PMID:12192004</ref> [[http://www.uniprot.org/uniprot/CDT1_MOUSE CDT1_MOUSE]] 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:11850834</ref> <ref>PMID:12192004</ref> <ref>PMID:14993212</ref> | + | [[https://www.uniprot.org/uniprot/GEMI_MOUSE GEMI_MOUSE]] Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle.<ref>PMID:9635433</ref> <ref>PMID:12192004</ref> Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (By similarity).<ref>PMID:9635433</ref> <ref>PMID:12192004</ref> [[https://www.uniprot.org/uniprot/CDT1_MOUSE CDT1_MOUSE]] 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:11850834</ref> <ref>PMID:12192004</ref> <ref>PMID:14993212</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zx/2zxx_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zx/2zxx_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Cho, Y]] | | [[Category: Cho, Y]] |
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| | [[Category: Cell cycle]] | | [[Category: Cell cycle]] |
| | [[Category: Cell cycle-replication complex]] | | [[Category: Cell cycle-replication complex]] |
| | + | [[Category: Coiled coil]] |
| | [[Category: Coiled-coil]] | | [[Category: Coiled-coil]] |
| | [[Category: Dna replication]] | | [[Category: Dna replication]] |
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| | [[Category: Phosphoprotein]] | | [[Category: Phosphoprotein]] |
| | [[Category: Proto-oncogene]] | | [[Category: Proto-oncogene]] |
| | + | [[Category: Ubl conjugation]] |
| Structural highlights
Function
[GEMI_MOUSE] Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle.[1] [2] Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (By similarity).[3] [4] [CDT1_MOUSE] 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.[5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
To maintain chromosome stability in eukaryotic cells, replication origins must be licensed by loading mini-chromosome maintenance (MCM2-7) complexes once and only once per cell cycle. This licensing control is achieved through the activities of geminin and cyclin-dependent kinases. Geminin binds tightly to Cdt1, an essential component of the replication licensing system, and prevents the inappropriate reinitiation of replication on an already fired origin. The inhibitory effect of geminin is thought to prevent the interaction between Cdt1 and the MCM helicase. Here we describe the crystal structure of the mouse geminin-Cdt1 complex using tGeminin (residues 79-157, truncated geminin) and tCdt1 (residues 172-368, truncated Cdt1). The amino-terminal region of a coiled-coil dimer of tGeminin interacts with both N-terminal and carboxy-terminal parts of tCdt1. The primary interface relies on the steric complementarity between the tGeminin dimer and the hydrophobic face of the two short N-terminal helices of tCdt1 and, in particular, Pro 181, Ala 182, Tyr 183, Phe 186 and Leu 189. The crystal structure, in conjunction with our biochemical data, indicates that the N-terminal region of tGeminin might be required to anchor tCdt1, and the C-terminal region of tGeminin prevents access of the MCM complex to tCdt1 through steric hindrance.
Structural basis for inhibition of the replication licensing factor Cdt1 by geminin.,Lee C, Hong B, Choi JM, Kim Y, Watanabe S, Ishimi Y, Enomoto T, Tada S, Kim Y, Cho Y Nature. 2004 Aug 19;430(7002):913-7. Epub 2004 Aug 1. PMID:15286659[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McGarry TJ, Kirschner MW. Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell. 1998 Jun 12;93(6):1043-53. PMID:9635433
- ↑ Yanagi K, Mizuno T, You Z, Hanaoka F. Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. J Biol Chem. 2002 Oct 25;277(43):40871-80. Epub 2002 Aug 20. PMID:12192004 doi:http://dx.doi.org/10.1074/jbc.M206202200
- ↑ McGarry TJ, Kirschner MW. Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell. 1998 Jun 12;93(6):1043-53. PMID:9635433
- ↑ Yanagi K, Mizuno T, You Z, Hanaoka F. Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. J Biol Chem. 2002 Oct 25;277(43):40871-80. Epub 2002 Aug 20. PMID:12192004 doi:http://dx.doi.org/10.1074/jbc.M206202200
- ↑ Arentson E, Faloon P, Seo J, Moon E, Studts JM, Fremont DH, Choi K. Oncogenic potential of the DNA replication licensing protein CDT1. Oncogene. 2002 Feb 14;21(8):1150-8. PMID:11850834 doi:http://dx.doi.org/10.1038/sj.onc.1205175
- ↑ Yanagi K, Mizuno T, You Z, Hanaoka F. Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. J Biol Chem. 2002 Oct 25;277(43):40871-80. Epub 2002 Aug 20. PMID:12192004 doi:http://dx.doi.org/10.1074/jbc.M206202200
- ↑ Sugimoto N, Tatsumi Y, Tsurumi T, Matsukage A, Kiyono T, Nishitani H, Fujita M. Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. J Biol Chem. 2004 May 7;279(19):19691-7. Epub 2004 Mar 1. PMID:14993212 doi:10.1074/jbc.M313175200
- ↑ Lee C, Hong B, Choi JM, Kim Y, Watanabe S, Ishimi Y, Enomoto T, Tada S, Kim Y, Cho Y. Structural basis for inhibition of the replication licensing factor Cdt1 by geminin. Nature. 2004 Aug 19;430(7002):913-7. Epub 2004 Aug 1. PMID:15286659 doi:10.1038/nature02813
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