8WG5

Cryo-EM structure of USP16 bound to H2AK119Ub nucleosome

Summary for 8WG5

• Entry DOI: 10.2210/pdb8wg5/pdb
• EMDB information: 37503
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 16, Histone H3.1, Histone H4, ... (8 entities in total)
• Functional Keywords: nucleosome complex, usp16, h2ak119ub, nuclear protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 279465.57

Authors

Ai, H.S.,He, Z.Z.,Deng, Z.H.,Liu, L. (deposition date: 2023-09-20, release date: 2023-12-27, Last modification date: 2024-11-27)

Primary citation

Ai, H.,He, Z.,Deng, Z.,Chu, G.C.,Shi, Q.,Tong, Z.,Li, J.B.,Pan, M.,Liu, L.
Structural and mechanistic basis for nucleosomal H2AK119 deubiquitination by single-subunit deubiquitinase USP16.
Nat.Struct.Mol.Biol., 31:1745-1755, 2024

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 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.

PubMed: 38918638
DOI: 10.1038/s41594-024-01342-2

Experimental method

ELECTRON MICROSCOPY (3.05 Å)