Structure of the human Bre1 complex bound to the nucleosome
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Nature communications - 15(2024), 1 vom: 22. März, Seite 2580 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Onishi, Shuhei [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
9007-49-2 |
|---|
| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 28.03.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-024-46910-8 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370090802 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370090802 | ||
| 003 | DE-627 | ||
| 005 | 20240329000925.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240324s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-024-46910-8 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1353.xml |
| 035 | |a (DE-627)NLM370090802 | ||
| 035 | |a (NLM)38519511 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Onishi, Shuhei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Structure of the human Bre1 complex bound to the nucleosome |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.03.2024 | ||
| 500 | |a Date Revised 28.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a DNA |2 NLM | |
| 650 | 7 | |a 9007-49-2 |2 NLM | |
| 650 | 7 | |a Histones |2 NLM | |
| 650 | 7 | |a Nucleosomes |2 NLM | |
| 650 | 7 | |a Ubiquitin-Protein Ligases |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 650 | 7 | |a RNF20 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 700 | 1 | |a Uchiyama, Kotone |e verfasserin |4 aut | |
| 700 | 1 | |a Sato, Ko |e verfasserin |4 aut | |
| 700 | 1 | |a Okada, Chikako |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Shunsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Hamada, Keisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Nishizawa, Tomohiro |e verfasserin |4 aut | |
| 700 | 1 | |a Nureki, Osamu |e verfasserin |4 aut | |
| 700 | 1 | |a Ogata, Kazuhiro |e verfasserin |4 aut | |
| 700 | 1 | |a Sengoku, Toru |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 15(2024), 1 vom: 22. März, Seite 2580 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g number:1 |g day:22 |g month:03 |g pages:2580 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-024-46910-8 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |e 1 |b 22 |c 03 |h 2580 | ||