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Title | Structural and mechanistic basis for nucleosomal H2AK119 deubiquitination by single-subunit deubiquitinase USP16. |
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Journal, issue, pages | Nat Struct Mol Biol, Year 2024 |
Publish date | Jun 25, 2024 |
Authors | Huasong Ai / Zaozhen He / Zhiheng Deng / Guo-Chao Chu / Qiang Shi / Zebin Tong / Jia-Bin Li / Man Pan / Lei Liu / |
PubMed Abstract | Epigenetic regulators have a crucial effect on gene expression based on their manipulation of histone modifications. Histone H2AK119 monoubiquitination (H2AK119Ub), a well-established hallmark in ...Epigenetic regulators have a crucial effect on gene expression based on their manipulation of histone modifications. Histone H2AK119 monoubiquitination (H2AK119Ub), a well-established hallmark in transcription repression, is dynamically regulated by the opposing activities of Polycomb repressive complex 1 (PRC1) and nucleosome deubiquitinases including the primary human USP16 and Polycomb repressive deubiquitinase (PR-DUB) complex. Recently, the catalytic mechanism for the multi-subunit PR-DUB complex has been described, but how the single-subunit USP16 recognizes the H2AK119Ub nucleosome and cleaves the ubiquitin (Ub) remains unknown. Here we report the cryo-EM structure of USP16-H2AK119Ub nucleosome complex, which unveils a fundamentally distinct mode of H2AK119Ub deubiquitination compared to PR-DUB, encompassing the nucleosome recognition pattern independent of the H2A-H2B acidic patch and the conformational heterogeneity in the Ub motif and the histone H2A C-terminal tail. Our work highlights the mechanism diversity of H2AK119Ub deubiquitination and provides a structural framework for understanding the disease-causing mutations of USP16. |
External links | Nat Struct Mol Biol / PubMed:38918638 |
Methods | EM (single particle) |
Resolution | 3.05 Å |
Structure data | EMDB-37503, PDB-8wg5: |
Source |
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Keywords | NUCLEAR PROTEIN / nucleosome complex / USP16 / H2AK119Ub |