4S3O

PCGF5-RING1B-UbcH5c complex

Summary for 4S3O

• Entry DOI: 10.2210/pdb4s3o/pdb
• Descriptor: Ubiquitin-conjugating enzyme E2 D3, E3 ubiquitin-protein ligase RING2, Polycomb group RING finger protein 5, ... (5 entities in total)
• Functional Keywords: e2, e3, ring domain, ubiquitin ring e3 ligase, ligase-transcription complex, ligase/transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane ; Peripheral membrane protein : P61077; Nucleus : Q99496 Q86SE9
• Total number of polymer chains: 6
• Total formula weight: 88357.96

Authors

Taherbhoy, A.M.,Cochran, A.G. (deposition date: 2015-03-23, release date: 2015-07-15, Last modification date: 2023-09-20)

Primary citation

Taherbhoy, A.M.,Huang, O.W.,Cochran, A.G.
BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase.
Nat Commun, 6:7621-7621, 2015

PubMed 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.

PubMed: 26151332
DOI: 10.1038/ncomms8621

Experimental method

X-RAY DIFFRACTION (2 Å)