2WVR

Human Cdt1:Geminin complex

Summary for 2WVR

• Entry DOI: 10.2210/pdb2wvr/pdb
• Related: 1T6F 1UII
• Descriptor: GEMININ, DNA REPLICATION FACTOR CDT1 (2 entities in total)
• Functional Keywords: replication, dna replication license, dna replication inhibitor, phosphoprotein, ubl conjugation, dna replication, dna-binding, polymorphism, proto-oncogene, nucleus, cell cycle, acetylation, coiled coil
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: Q9H211
• Total number of polymer chains: 3
• Total formula weight: 107733.75

Authors

De Marco, V.,Perrakis, A. (deposition date: 2009-10-19, release date: 2009-10-27, Last modification date: 2024-05-08)

Primary citation

De Marco, V.,Gillespie, P.J.,Li, A.,Karantzelis, N.,Christodoulou, E.,Klompmaker, R.,Van Gerwen, S.,Fish, A.,Petoukhov, M.V.,Iliou, M.S.,Lygerou, Z.,Medema, R.H.,Blow, J.J.,Svergun, D.I.,Taraviras, S.,Perrakis, A.
Quaternary Structure of the Human Cdt1-Geminin Complex Regulates DNA Replication Licensing.
Proc.Natl.Acad.Sci.USA, 106:19807-, 2009

PubMed Abstract: 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.

PubMed: 19906994
DOI: 10.1073/PNAS.0905281106

Experimental method

X-RAY DIFFRACTION (3.3 Å)