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| Subject Categories: Chromatin & Transcription | Structural Biology |
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| The EMBO Journal
(2006) 25, 2465–2474, doi:10.1038/sj.emboj.7601144 Published online 18 May 2006 |
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| Structure and E3-ligase activity of the Ring–Ring complex of Polycomb proteins Bmi1 and Ring1b |
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| Gretel Buchwald1, Petra van der Stoop2, Oliver Weichenrieder1, Anastassis Perrakis1, Maarten van Lohuizen2 and Titia K Sixma1 |
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1 Division of Molecular Carcinogenesis and Center for Biomedical Genetics, Netherlands Cancer Institute, Amsterdam, Netherlands 2 Division of Molecular Genetics and Center for Biomedical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands To whom correspondence should be addressed Titia K Sixma, Division of Molecular Carcinogenesis and Center for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands. Tel.: +31 20 5121959; Fax: +31 20 5121954; E-mail: t.sixma@nki.nl Received 19 December 2005; Accepted 21 April 2006; Published online 18 May 2006. |
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| Abstract |
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| Polycomb group proteins Ring1b and Bmi1 (B-cell-specific Moloney murine leukaemia virus integration site 1) are critical components of the chromatin modulating PRC1 complex. Histone H2A ubiquitination by the PRC1 complex strongly depends on the Ring1b protein. Here we show that the E3-ligase activity of Ring1b on histone H2A is enhanced by Bmi1 in vitro. The N-terminal Ring-domains are sufficient for this activity and Ring1a can replace Ring1b. E2 enzymes UbcH5a, b, c or UbcH6 support this activity with varying processivity and selectivity. All four E2s promote autoubiquitination of Ring1b without affecting E3-ligase activity. We solved the crystal structure of the Ring–Ring heterodimeric complex of Ring1b and Bmi1. In the structure the arrangement of the Ring-domains is similar to another H2A E3 ligase, the BRCA1/BARD1 complex, but complex formation depends on an N-terminal arm of Ring1b that embraces the Bmi1 Ring-domain. Mutation of a critical residue in the E2/E3 interface shows that catalytic activity resides in Ring1b and not in Bmi1. These data provide a foundation for understanding the critical enzymatic activity at the core of the PRC1 polycomb complex, which is implicated in stem cell maintenance and cancer. |
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| Keywords: Bmi1, crystal structure, E3 ligase, polycomb, Ring1b |
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