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.