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| | ==Crystal structure of Geminin coiled-coil domain== | | ==Crystal structure of Geminin coiled-coil domain== |
| - | <StructureSection load='1uii' size='340' side='right' caption='[[1uii]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='1uii' size='340' side='right'caption='[[1uii]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1uii]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UII OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UII FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1uii]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UII OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UII FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GMNN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</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=1uii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uii OCA], [http://pdbe.org/1uii PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uii RCSB], [http://www.ebi.ac.uk/pdbsum/1uii 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=1uii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uii OCA], [https://pdbe.org/1uii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uii RCSB], [https://www.ebi.ac.uk/pdbsum/1uii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uii ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GEMI_HUMAN GEMI_HUMAN]] 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:14993212</ref> <ref>PMID:22615398</ref> Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control.<ref>PMID:9635433</ref> <ref>PMID:14993212</ref> <ref>PMID:22615398</ref> | + | [https://www.uniprot.org/uniprot/GEMI_HUMAN GEMI_HUMAN] 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:14993212</ref> <ref>PMID:22615398</ref> Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control.<ref>PMID:9635433</ref> <ref>PMID:14993212</ref> <ref>PMID:22615398</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/ui/1uii_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ui/1uii_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: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Robinson, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Swaminathan, K]] | + | [[Category: Robinson H]] |
| - | [[Category: Yuan, P]] | + | [[Category: Swaminathan K]] |
| - | [[Category: Cell cycle]] | + | [[Category: Yuan P]] |
| - | [[Category: Dna replication]]
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| - | [[Category: Geminin]]
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| Structural highlights
Function
GEMI_HUMAN 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] [3] Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control.[4] [5] [6]
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
Geminin is a cellular protein that associates with Cdt1 and inhibits Mcm2-7 loading during S phase. It prevents multiple cycles of replication per cell cycle and prevents episome replication. It also directly inhibits the HoxA11 transcription factor. Here we report that geminin forms a parallel coiled-coil homodimer with atypical residues in the dimer interface. Point mutations that disrupt the dimerization abolish interaction with Cdt1 and inhibition of replication. An array of glutamic acid residues on the coiled-coil domain surface interacts with positive charges in the middle of Cdt1. An adjoining region interacts independently with the N-terminal 100 residues of Cdt1. Both interactions are essential for replication inhibition. The negative residues on the coiled-coil domain and a different part of geminin are also required for interaction with HoxA11. Therefore a rigid cylinder with negative surface charges is a critical component of a bipartite interaction interface between geminin and its cellular targets.
A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition.,Saxena S, Yuan P, Dhar SK, Senga T, Takeda D, Robinson H, Kornbluth S, Swaminathan K, Dutta A Mol Cell. 2004 Jul 23;15(2):245-58. PMID:15260975[7]
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
- ↑ 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
- ↑ Zhou B, Liu C, Xu Z, Zhu G. Structural basis for homeodomain recognition by the cell-cycle regulator Geminin. Proc Natl Acad Sci U S A. 2012 May 21. PMID:22615398 doi:10.1073/pnas.1200874109
- ↑ McGarry TJ, Kirschner MW. Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell. 1998 Jun 12;93(6):1043-53. PMID:9635433
- ↑ 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
- ↑ Zhou B, Liu C, Xu Z, Zhu G. Structural basis for homeodomain recognition by the cell-cycle regulator Geminin. Proc Natl Acad Sci U S A. 2012 May 21. PMID:22615398 doi:10.1073/pnas.1200874109
- ↑ Saxena S, Yuan P, Dhar SK, Senga T, Takeda D, Robinson H, Kornbluth S, Swaminathan K, Dutta A. A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. Mol Cell. 2004 Jul 23;15(2):245-58. PMID:15260975 doi:10.1016/j.molcel.2004.06.045
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