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| | ==Crystal Structure of the Coiled-coil Dimerization Motif of Geminin== | | ==Crystal Structure of the Coiled-coil Dimerization Motif of Geminin== |
| - | <StructureSection load='1t6f' size='340' side='right' caption='[[1t6f]], [[Resolution|resolution]] 1.47Å' scene=''> | + | <StructureSection load='1t6f' size='340' side='right'caption='[[1t6f]], [[Resolution|resolution]] 1.47Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1t6f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T6F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1t6f]] 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=1T6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T6F 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=1t6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t6f OCA], [http://pdbe.org/1t6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t6f RCSB], [http://www.ebi.ac.uk/pdbsum/1t6f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t6f ProSAT]</span></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]] 1.47Å</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=1t6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t6f OCA], [https://pdbe.org/1t6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t6f RCSB], [https://www.ebi.ac.uk/pdbsum/1t6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t6f 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]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Auge, M T]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Dumas, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Guichou, J F]] | + | [[Category: Auge M-T]] |
| - | [[Category: Maiorano, D]] | + | [[Category: Dumas C]] |
| - | [[Category: Mechali, M]] | + | [[Category: Guichou J-F]] |
| - | [[Category: Padilla, A]] | + | [[Category: Maiorano D]] |
| - | [[Category: Thepaut, M]] | + | [[Category: Mechali M]] |
| - | [[Category: Cell cycle]]
| + | [[Category: Padilla A]] |
| - | [[Category: Coiled-coil]]
| + | [[Category: Thepaut M]] |
| 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
We have determined the crystal structure of the coiled-coil domain of human geminin, a DNA synthesis inhibitor in higher eukaryotes. We show that a peptide encompassing the five heptad repeats of the geminin leucine zipper (LZ) domain is a dimeric parallel coiled coil characterized by a unique pattern of internal polar residues and a negatively charged surface that may target the basic domain of interacting partners. We show that the LZ domain itself is not sufficient to inhibit DNA synthesis but upstream and downstream residues are required. Analysis of a functional form of geminin by density sedimentation indicates an oligomeric structure. X-ray solution scattering experiments performed on a non-functional form of geminin having upstream basic residues and the LZ domain show a tetramer structure. Altogether, these results give a consistent identification and mapping of geminin interacting regions onto structurally important domains. They also suggest that oligomerization properties of geminin may be implicated in its inhibitory activity of DNA synthesis.
Crystal structure of the coiled-coil dimerization motif of geminin: structural and functional insights on DNA replication regulation.,Thepaut M, Maiorano D, Guichou JF, Auge MT, Dumas C, Mechali M, Padilla A J Mol Biol. 2004 Sep 3;342(1):275-87. PMID:15313623[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
- ↑ Thepaut M, Maiorano D, Guichou JF, Auge MT, Dumas C, Mechali M, Padilla A. Crystal structure of the coiled-coil dimerization motif of geminin: structural and functional insights on DNA replication regulation. J Mol Biol. 2004 Sep 3;342(1):275-87. PMID:15313623 doi:10.1016/j.jmb.2004.06.065
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