Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex.
Polycomb group proteins Bmi-1 and Ring1B are core subunits of the PRC1 complex, which plays important roles in the regulation of Hox gene expression, X-chromosome inactivation, tumorigenesis, and stem cell self-renewal. The RING finger protein Ring1B is an E3 ligase that participates in the ubiquitination of lysine 119 of histone H2A, and the binding of Bmi-1 stimulates the E3 ligase activity. We have mapped the regions of Bmi-1 and Ring1B required for efficient ubiquitin transfer and determined a 2.5-A structure of the Bmi-1-Ring1B core domain complex. The structure reveals that Ring1B "hugs" Bmi-1 through extensive RING domain contacts and its N-terminal tail wraps around Bmi-1. The two regions of interaction have a synergistic effect on the E3 ligase activity. Our analyses suggest a model where the Bmi-1-Ring1B complex stabilizes the interaction between the E2 enzyme and the nucleosomal substrate to allow efficient ubiquitin transfer.
Li
Zhizhong
Z
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Cao
Ru
R
Wang
Ming
M
Myers
Michael P
MP
Zhang
Yi
Y
Xu
Rui-Ming
RM
D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry*; D063150:Polycomb Repressive Complex 1; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D012097:Repressor Proteins / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry*
C069077:BMI1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human; D044767:Ubiquitin-Protein Ligases