4bry
From Proteopedia
The Idas:Geminin heterodimeric parallel coiled-coil
Structural highlights
FunctionGEMI_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.[1] [2] [3] Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control.[4] [5] [6] Publication Abstract from PubMedGeminin 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 (~30nM), but with notably different thermodynamic properties. Consistently, in Xenopus egg extracts, Idas:Geminin is less active in licensing inhibition compared to 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. The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing.,Caillat C, Pefani ED, Gillespie PJ, Taraviras S, Blow JJ, Lygerou Z, Perrakis A J Biol Chem. 2013 Oct 2. PMID:24064211[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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