View source for 2wvr


==Human Cdt1:Geminin complex==
<StructureSection load='2wvr' size='340' side='right'caption='[[2wvr]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
</table>
== Function ==
[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 ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wv/2wvr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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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== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2wvr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: De Marco V]]
[[Category: Perrakis A]]