Structural basis of the histone ubiquitination read-write mechanism of RYBP-PRC1

Nat Struct Mol Biol. 2024 Jul;31(7):1023-1027. doi: 10.1038/s41594-024-01258-x. Epub 2024 Mar 25.

Abstract

Histone H2A monoubiquitination (H2Aub1) by the PRC1 subunit RING1B entails a positive feedback loop, mediated by the RING1B-interacting protein RYBP. We uncover that human RYBP-PRC1 binds unmodified nucleosomes via RING1B but H2Aub1-modified nucleosomes via RYBP. RYBP interactions with both ubiquitin and the nucleosome acidic patch create the high binding affinity that favors RYBP- over RING1B-directed PRC1 binding to H2Aub1-modified nucleosomes; this enables RING1B to monoubiquitinate H2A in neighboring unmodified nucleosomes.

MeSH terms

  • Cell Cycle Proteins
  • Histones* / chemistry
  • Histones* / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Models, Molecular
  • Nucleosomes* / chemistry
  • Nucleosomes* / metabolism
  • Polycomb Repressive Complex 1* / chemistry
  • Polycomb Repressive Complex 1* / metabolism
  • Protein Binding
  • Repressor Proteins* / chemistry
  • Repressor Proteins* / metabolism
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination*

Substances

  • Cell Cycle Proteins
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Nucleosomes
  • Polycomb Repressive Complex 1
  • PRC1 protein, human
  • Repressor Proteins
  • RNF2 protein, human
  • Ubiquitin-Protein Ligases
  • RYBP protein, human