EMD-34432

Single-particle
3.8 Å
EMD-34432 Deposition: 04/10/2022
Map released: 01/02/2023
Last modified: 19/04/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-34432

Cryo-EM structure of BAP1-ASXL1 bound to nucleosome

EMD-34432

Single-particle
3.8 Å
EMD-34432 Deposition: 04/10/2022
Map released: 01/02/2023
Last modified: 19/04/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Cryo-EM structure of BAP1-ASXL1 bound to nucleosome

Deposition Authors: Ge W, Yu C, Xu RM
Basis of the H2AK119 specificity of the Polycomb repressive deubiquitinase.
Ge W, Yu C, Li J , Yu Z, Li X, Zhang Y , Liu CP, Li Y , Tian C, Zhang X , Li G, Zhu B , Xu RM
(2023) Nature , 616 , 176 - 182
PUBMED: 36991118
DOI: doi:10.1038/s41586-023-05841-y
ISSN: 1476-4687
ASTM: NATUAS
Abstract:
Repression of gene expression by protein complexes of the Polycomb group is a fundamental mechanism that governs embryonic development and cell-type specification1-3. The Polycomb repressive deubiquitinase (PR-DUB) complex removes the ubiquitin moiety from monoubiquitinated histone H2A K119 (H2AK119ub1) on the nucleosome4, counteracting the ubiquitin E3 ligase activity of Polycomb repressive complex 1 (PRC1)5 to facilitate the correct silencing of genes by Polycomb proteins and safeguard active genes from inadvertent silencing by PRC1 (refs. 6-9). The intricate biological function of PR-DUB requires accurate targeting of H2AK119ub1, but PR-DUB can deubiquitinate monoubiquitinated free histones and peptide substrates indiscriminately; the basis for its exquisite nucleosome-dependent substrate specificity therefore remains unclear. Here we report the cryo-electron microscopy structure of human PR-DUB, composed of BAP1 and ASXL1, in complex with the chromatosome. We find that ASXL1 directs the binding of the positively charged C-terminal extension of BAP1 to nucleosomal DNA and histones H3-H4 near the dyad, an addition to its role in forming the ubiquitin-binding cleft. Furthermore, a conserved loop segment of the catalytic domain of BAP1 is situated near the H2A-H2B acidic patch. This distinct nucleosome-binding mode displaces the C-terminal tail of H2A from the nucleosome surface, and endows PR-DUB with the specificity for H2AK119ub1.