2wvr

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{{STRUCTURE_2wvr| PDB=2wvr | SCENE= }}
 
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===HUMAN CDT1:GEMININ COMPLEX===
 
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{{ABSTRACT_PUBMED_19906994}}
 
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==Disease==
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==Human Cdt1:Geminin complex==
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[[http://www.uniprot.org/uniprot/CDT1_HUMAN CDT1_HUMAN]] Defects in CDT1 are the cause of Meier-Gorlin syndrome type 4 (MGORS4) [MIM:[http://omim.org/entry/613804 613804]]. MGORS4 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.<ref>PMID:21358632</ref><ref>PMID:21358631</ref>
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<StructureSection load='2wvr' size='340' side='right'caption='[[2wvr]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2wvr]] is a 3 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=2WVR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WVR FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wvr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wvr OCA], [https://pdbe.org/2wvr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wvr RCSB], [https://www.ebi.ac.uk/pdbsum/2wvr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wvr ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wv/2wvr_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wvr ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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All organisms need to ensure that no DNA segments are rereplicated in a single cell cycle. Eukaryotes achieve this through a process called origin licensing, which involves tight spatiotemporal control of the assembly of prereplicative complexes (pre-RCs) onto chromatin. Cdt1 is a key component and crucial regulator of pre-RC assembly. In higher eukaryotes, timely inhibition of Cdt1 by Geminin is essential to prevent DNA rereplication. Here, we address the mechanism of DNA licensing inhibition by Geminin, by combining X-ray crystallography, small-angle X-ray scattering, and functional studies in Xenopus and mammalian cells. Our findings show that the Cdt1:Geminin complex can exist in two distinct forms, a "permissive" heterotrimer and an "inhibitory" heterohexamer. Specific Cdt1 residues, buried in the heterohexamer, are important for licensing. We postulate that the transition between the heterotrimer and the heterohexamer represents a molecular switch between licensing-competent and licensing-defective states.
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==Function==
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Quaternary structure of the human Cdt1-Geminin complex regulates DNA replication licensing.,De Marco V, Gillespie PJ, Li A, Karantzelis N, Christodoulou E, Klompmaker R, van Gerwen S, Fish A, Petoukhov MV, Iliou MS, Lygerou Z, Medema RH, Blow JJ, Svergun DI, Taraviras S, Perrakis A Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19807-12. Epub 2009 Nov 11. PMID:19906994<ref>PMID:19906994</ref>
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[[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> [[http://www.uniprot.org/uniprot/CDT1_HUMAN CDT1_HUMAN]] 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:11125146</ref><ref>PMID:21856198</ref><ref>PMID:14672932</ref><ref>PMID:14993212</ref>[UniProtKB:Q8R4E9]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[2wvr]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WVR OCA].
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</div>
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<div class="pdbe-citations 2wvr" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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<ref group="xtra">PMID:019906994</ref><references group="xtra"/><references/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Marco, V De.]]
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[[Category: Large Structures]]
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[[Category: Perrakis, A.]]
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[[Category: De Marco V]]
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[[Category: Cell cycle]]
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[[Category: Perrakis A]]
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[[Category: Dna replication]]
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[[Category: Dna replication inhibitor]]
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[[Category: Dna replication license]]
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[[Category: Dna-binding]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Proto-oncogene]]
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[[Category: Replication]]
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Current revision

Human Cdt1:Geminin complex

PDB ID 2wvr

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