Structure and E3-ligase activity of the Ring-Ring complex of Polycomb proteins Bmi1 and Ring1b

Polycomb group proteins Ring1b and Bmi1 ( B ‐cell‐specific M oloney murine leukaemia virus i ntegration 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 act...

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Veröffentlicht in:	The EMBO journal Jg. 25; H. 11; S. 2465 - 2474
Hauptverfasser:	Buchwald, Gretel, van der Stoop, Petra, Weichenrieder, Oliver, Perrakis, Anastassis, van Lohuizen, Maarten, Sixma, Titia K
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Chichester, UK John Wiley & Sons, Ltd 07.06.2006 Nature Publishing Group UK Springer Nature B.V
Schlagworte:	Amino Acid Sequence Animals Biomedical research Bmi1 Breast cancer Chromatin Crystal structure Crystallography, X-Ray Dimerization E3 ligase EMBO09 EMBO40 Enzymatic activity Female Histones - metabolism Humans Leukemia Mice Models, Molecular Molecular biology Molecular Sequence Data Multiprotein Complexes Murine leukemia virus Mutation Nuclear Proteins - chemistry Nuclear Proteins - genetics Nuclear Proteins - metabolism polycomb Polycomb Repressive Complex 1 Protein Conformation Proteins Proto-Oncogene Proteins - chemistry Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Recombinant Fusion Proteins - chemistry Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Repressor Proteins - chemistry Repressor Proteins - genetics Repressor Proteins - metabolism Ring1b Sequence Alignment Stem cells Ubiquitin - metabolism Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism crystal structure Ring1b E3 ligase Bmi1 polycomb
ISSN:	0261-4189, 1460-2075
Online-Zugang:	Volltext
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Zusammenfassung:	Polycomb group proteins Ring1b and Bmi1 ( B ‐cell‐specific M oloney murine leukaemia virus i ntegration 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.
Bibliographie:	Supplementary Figure 1Supplementary Figure 2Supplementary Information ark:/67375/WNG-WBNG4GPB-0 istex:8883A86F24CB3645A0F3B050E76FFAC0DA2A295B ArticleID:EMBJ7601144 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0261-4189 1460-2075
DOI:	10.1038/sj.emboj.7601144