8H1T

Cryo-EM structure of BAP1-ASXL1 bound to chromatosome

8H1T の概要

• エントリーDOI: 10.2210/pdb8h1t/pdb
• EMDBエントリー: 34431 35179 35180 35181 35182
• 分子名称: Histone H3.1, Polycomb group protein ASXL1, Histone H4, ... (10 entities in total)
• 機能のキーワード: nucleosome, histone deubiquitination, chromatin, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 379323.15

構造登録者

Ge, W.,Yu, C.,Xu, R.M. (登録日: 2022-10-04, 公開日: 2023-02-01, 最終更新日: 2024-07-03)

主引用文献

Ge, W.,Yu, C.,Li, J.,Yu, Z.,Li, X.,Zhang, Y.,Liu, C.P.,Li, Y.,Tian, C.,Zhang, X.,Li, G.,Zhu, B.,Xu, R.M.
Basis of the H2AK119 specificity of the Polycomb repressive deubiquitinase.
Nature, 616:176-182, 2023

PubMed Abstract: Repression of gene expression by protein complexes of the Polycomb group is a fundamental mechanism that governs embryonic development and cell-type specification. The Polycomb repressive deubiquitinase (PR-DUB) complex removes the ubiquitin moiety from monoubiquitinated histone H2A K119 (H2AK119ub1) on the nucleosome, counteracting the ubiquitin E3 ligase activity of Polycomb repressive complex 1 (PRC1) to facilitate the correct silencing of genes by Polycomb proteins and safeguard active genes from inadvertent silencing by PRC1 (refs. ). 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.

PubMed: 36991118
DOI: 10.1038/s41586-023-05841-y

実験手法

ELECTRON MICROSCOPY (3 Å)