2wvr

Human Cdt1:Geminin complex

spinqualitylabelsall models 2wvr, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wvr is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control. 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 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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