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TitleStructure of the human Bre1 complex bound to the nucleosome.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 2580, Year 2024
Publish dateMar 22, 2024
AuthorsShuhei Onishi / Kotone Uchiyama / Ko Sato / Chikako Okada / Shunsuke Kobayashi / Keisuke Hamada / Tomohiro Nishizawa / Osamu Nureki / Kazuhiro Ogata / Toru Sengoku /
PubMed AbstractHistone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of ...Histone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of Bre1A/RNF20 and Bre1B/RNF40. The Bre1 proteins generally function as tumor suppressors, while in certain cancers, they facilitate cancer cell proliferation. To obtain structural insights of H2BK120 ubiquitination and its regulation, we report the cryo-electron microscopy structure of the human Bre1 complex bound to the nucleosome. The two RING domains of Bre1A and Bre1B recognize the acidic patch and the nucleosomal DNA phosphates around SHL 6.0-6.5, which are ideally located to recruit the E2 enzyme and ubiquitin for H2BK120-specific ubiquitination. Mutational experiments suggest that the two RING domains bind in two orientations and that ubiquitination occurs when Bre1A binds to the acidic patch. Our results provide insights into the H2BK120-specific ubiquitination by the Bre1 proteins and suggest that H2B monoubiquitination can be regulated by nuclesomal DNA flexibility.
External linksNat Commun / PubMed:38519511 / PubMed Central
MethodsEM (single particle)
Resolution2.51 - 2.81 Å
Structure data

34274

8gui

8guj

EMDB-34274: Bre1-nucleosome complex
PDB-8gui: Bre1-nucleosome complex (Model I)
PDB-8guj: Bre1-nucleosome complex (Model II)
Method: EM (single particle) / Resolution: 2.81 Å

34275

8guk

EMDB-34275, PDB-8guk:
Human nucleosome core particle (free form)
Method: EM (single particle) / Resolution: 2.51 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsGENE REGULATION/DNA / transcription / ubiquitin ligase / cancer / chromatin / GENE REGULATION / GENE REGULATION-DNA complex

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