Recognition of UbcH5c and the nucleosome by the Bmi1/Ring1b ubiquitin ligase complex.
The Polycomb repressive complex 1 (PRC1) mediates gene silencing, in part by monoubiquitination of histone H2A on lysine 119 (uH2A). Bmi1 and Ring1b are critical components of PRC1 that heterodimerize via their N-terminal RING domains to form an active E3 ubiquitin ligase. We have determined the crystal structure of a ... complex between the Bmi1/Ring1b RING-RING heterodimer and the E2 enzyme UbcH5c and find that UbcH5c interacts with Ring1b only, in a manner fairly typical of E2-E3 interactions. However, we further show that the Bmi1/Ring1b RING domains bind directly to duplex DNA through a basic surface patch unique to the Bmi1/Ring1b RING-RING dimer. Mutation of residues on this interaction surface leads to a loss of H2A ubiquitination activity. Computational modelling of the interface between Bmi1/Ring1b-UbcH5c and the nucleosome suggests that Bmi1/Ring1b interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve specific monoubiquitination of H2A. Our results point to a novel mechanism of substrate recognition, and control of product formation, by Bmi1/Ring1b.
Mesh Terms:
Crystallography, X-Ray, DNA, Fungal, Dimerization, Gene Expression Regulation, Fungal, Gene Silencing, Histones, Humans, Hydrogen Bonding, Models, Chemical, Models, Molecular, Multiprotein Complexes, Mutagenesis, Site-Directed, Nucleosomes, Protein Binding, Protein Conformation, Protein Interaction Mapping, Protein Processing, Post-Translational, Protein Structure, Tertiary, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sodium Chloride, Substrate Specificity, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitination
Crystallography, X-Ray, DNA, Fungal, Dimerization, Gene Expression Regulation, Fungal, Gene Silencing, Histones, Humans, Hydrogen Bonding, Models, Chemical, Models, Molecular, Multiprotein Complexes, Mutagenesis, Site-Directed, Nucleosomes, Protein Binding, Protein Conformation, Protein Interaction Mapping, Protein Processing, Post-Translational, Protein Structure, Tertiary, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sodium Chloride, Substrate Specificity, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitination
EMBO J.
Date: Jul. 21, 2011
PubMed ID: 21772249
View in: Pubmed Google Scholar
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