4BRY

The Idas:Geminin heterodimeric parallel coiled-coil

Summary for 4BRY

• Entry DOI: 10.2210/pdb4bry/pdb
• Descriptor: GEMININ, MULTICILIN, TETRAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: cell cycle, dna replication licensing
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: O75496; Nucleus: D6RGH6
• Total number of polymer chains: 2
• Total formula weight: 18340.46

Authors

Caillat, C.,Perrakis, A. (deposition date: 2013-06-06, release date: 2013-10-02, Last modification date: 2023-12-20)

Primary citation

Caillate, C.,Pefani, E.D.,Gillespie, P.J.,Taraviras, S.,Blow, J.J.,Lygerou, Z.,Perrakis, A.
The Geminin and Idas Coiled Coils Preferentially Form a Heterodimer that Inhibits Geminin Function in DNA Replication Licensing
J.Biol.Chem., 288:31624-, 2013

PubMed Abstract: Geminin is an important regulator of proliferation and differentiation in metazoans, which predominantly inhibits the DNA replication licensing factor Cdt1, preventing genome over-replication. We show that Geminin preferentially forms stable coiled-coil heterodimers with its homologue, Idas. In contrast to Idas-Geminin heterodimers, Idas homodimers are thermodynamically unstable and are unlikely to exist as a stable macromolecule under physiological conditions. The crystal structure of the homology regions of Idas in complex with Geminin showed a tight head-to-head heterodimeric coiled-coil. This Idas-Geminin heterodimer binds Cdt1 less strongly than Geminin-Geminin, still with high affinity (∼30 nm), but with notably different thermodynamic properties. Consistently, in Xenopus egg extracts, Idas-Geminin is less active in licensing inhibition compared with a Geminin-Geminin homodimer. In human cultured cells, ectopic expression of Idas leads to limited over-replication, which is counteracted by Geminin co-expression. The properties of the Idas-Geminin complex suggest it as the functional form of Idas and provide a possible mechanism to modulate Geminin activity.

PubMed: 24064211
DOI: 10.1074/JBC.M113.491928

Experimental method

X-RAY DIFFRACTION (2.89 Å)