8TXW

Cryo-EM structure of the human nucleosome core particle ubiquitylated at histone H2A K15 in complex with RNF168 (Class 2)

8TXW の概要

• エントリーDOI: 10.2210/pdb8txw/pdb
• EMDBエントリー: 41707
• 分子名称: Histone H3.1, Histone H4, Histone H2B type 1-C/E/F/G/I, ... (8 entities in total)
• 機能のキーワード: nucleosome core particle, chromatin, rnf168, miu2-lrm domains, dna repair, dna double-strand break, homologous recombination, brca1-bard1, 53bp1, ubiquitin, structural protein-dna-transferase complex, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 275187.91

構造登録者

Hu, Q.,Botuyan, M.V.,Zhao, D.,Cui, G.,Mer, G. (登録日: 2023-08-24, 公開日: 2024-01-17, 最終更新日: 2024-10-09)

主引用文献

Hu, Q.,Zhao, D.,Cui, G.,Bhandari, J.,Thompson, J.R.,Botuyan, M.V.,Mer, G.
Mechanisms of RNF168 nucleosome recognition and ubiquitylation.
Mol.Cell, 84:839-853.e12, 2024

PubMed Abstract: RNF168 plays a central role in the DNA damage response (DDR) by ubiquitylating histone H2A at K13 and K15. These modifications direct BRCA1-BARD1 and 53BP1 foci formation in chromatin, essential for cell-cycle-dependent DNA double-strand break (DSB) repair pathway selection. The mechanism by which RNF168 catalyzes the targeted accumulation of H2A ubiquitin conjugates to form repair foci around DSBs remains unclear. Here, using cryoelectron microscopy (cryo-EM), nuclear magnetic resonance (NMR) spectroscopy, and functional assays, we provide a molecular description of the reaction cycle and dynamics of RNF168 as it modifies the nucleosome and recognizes its ubiquitylation products. We demonstrate an interaction of a canonical ubiquitin-binding domain within full-length RNF168, which not only engages ubiquitin but also the nucleosome surface, clarifying how such site-specific ubiquitin recognition propels a signal amplification loop. Beyond offering mechanistic insights into a key DDR protein, our study aids in understanding site specificity in both generating and interpreting chromatin ubiquitylation.

PubMed: 38242129
DOI: 10.1016/j.molcel.2023.12.036

実験手法

ELECTRON MICROSCOPY (3.6 Å)