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Nat Commun. 2015 Jul 7;6:7621. doi: 10.1038/ncomms8621.

BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase.

Author information

1
Department of Early Discovery Biochemistry, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.

Abstract

Polycomb repressive complex 1 (PRC1) is required for ubiquitination of histone H2A lysine 119, an epigenetic mark associated with repression of genes important in developmental regulation. The E3 ligase activity of PRC1 resides in the RING1A/B subunit when paired with one of six PCGF partners. The best known of these is the oncogene BMI1/PCGF4. We find that canonical PRC1 E3 ligases such as PCGF4-RING1B have intrinsically very low enzymatic activity compared with non-canonical PRC1 RING dimers. The structure of a high-activity variant in complex with E2 (PCGF5-RING1B-UbcH5c) reveals only subtle differences from an earlier PCGF4 complex structure. However, two charged residues present in the modelled interface with E2-conjugated ubiquitin prove critical: in BMI1/PCGF4, these residues form a salt bridge that may limit efficient ubiquitin transfer. The intrinsically low activity of the PCGF4-RING1B heterodimer is offset by a relatively favourable interaction with nucleosome substrates, resulting in an efficient site-specific monoubiquitination.

PMID:
26151332
DOI:
10.1038/ncomms8621
[Indexed for MEDLINE]

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