Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome

Robert K. McGinty, Ryan C. Henrici, Song Tan

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

The Polycomb group of epigenetic enzymes represses expression of developmentally regulated genes in many eukaryotes. This group includes the Polycomb repressive complex 1 (PRC1), which ubiquitylates nucleosomal histone H2A Lys 119 using its E3 ubiquitin ligase subunits, Ring1B and Bmi1, together with an E2 ubiquitin-conjugating enzyme, UbcH5c. However, the molecular mechanism of nucleosome substrate recognition by PRC1 or other chromatin enzymes is unclear. Here we present the crystal structure of the human Ring1B-Bmi1-UbcH5c E3-E2 complex (the PRC1 ubiquitylation module) bound to its nucleosome core particle substrate. The structure shows how a chromatin enzyme achieves substrate specificity by interacting with several nucleosome surfaces spatially distinct from the site of catalysis. Our structure further reveals an unexpected role for the ubiquitin E2 enzyme in substrate recognition, and provides insight into how the related histone H2A E3 ligase, BRCA1, interacts with and ubiquitylates the nucleosome.

Original languageEnglish (US)
Pages (from-to)591-596
Number of pages6
JournalNature
Volume514
Issue number7524
DOIs
StatePublished - Oct 30 2014

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Polycomb Repressive Complex 1
Nucleosomes
Ubiquitination
Ubiquitin-Protein Ligases
Enzymes
Histones
Chromatin
Ubiquitin-Conjugating Enzymes
Ubiquitin
Substrate Specificity
Eukaryota
Catalysis
Epigenomics
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

McGinty, Robert K. ; Henrici, Ryan C. ; Tan, Song. / Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. In: Nature. 2014 ; Vol. 514, No. 7524. pp. 591-596.
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Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. / McGinty, Robert K.; Henrici, Ryan C.; Tan, Song.

In: Nature, Vol. 514, No. 7524, 30.10.2014, p. 591-596.

Research output: Contribution to journalArticle

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