5VF0

Solution NMR structure of human RAD18 (198-240) in complex with ubiquitin

5VF0 の概要

• エントリーDOI: 10.2210/pdb5vf0/pdb
• 関連するPDBエントリー: 5VEY
• NMR情報: BMRB: 30276
• 分子名称: Polyubiquitin-B, E3 ubiquitin-protein ligase RAD18, ZINC ION (3 entities in total)
• 機能のキーワード: ubiquitin ligase, ubiquitin, nucleosome, dna damage response, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13867.26

構造登録者

Hu, Q.,Botuyan, M.V.,Mer, G. (登録日: 2017-04-06, 公開日: 2017-05-17, 最終更新日: 2024-05-15)

主引用文献

Hu, Q.,Botuyan, M.V.,Cui, G.,Zhao, D.,Mer, G.
Mechanisms of Ubiquitin-Nucleosome Recognition and Regulation of 53BP1 Chromatin Recruitment by RNF168/169 and RAD18.
Mol. Cell, 66:473-487.e9, 2017

PubMed Abstract: The protein 53BP1 plays a central regulatory role in DNA double-strand break repair. 53BP1 relocates to chromatin by recognizing RNF168-mediated mono-ubiquitylation of histone H2A Lys15 in the nucleosome core particle dimethylated at histone H4 Lys20 (NCP-ubme). 53BP1 relocation is terminated by ubiquitin ligases RNF169 and RAD18 via unknown mechanisms. Using nuclear magnetic resonance (NMR) spectroscopy and biochemistry, we show that RNF169 bridges ubiquitin and histone surfaces, stabilizing a pre-existing ubiquitin orientation in NCP-ubme to form a high-affinity complex. This conformational selection mechanism contrasts with the low-affinity binding mode of 53BP1, and it ensures 53BP1 displacement by RNF169 from NCP-ubme. We also show that RAD18 binds tightly to NCP-ubme through a ubiquitin-binding domain that contacts ubiquitin and nucleosome surfaces accessed by 53BP1. Our work uncovers diverse ubiquitin recognition mechanisms in the nucleosome, explaining how RNF168, RNF169, and RAD18 regulate 53BP1 chromatin recruitment and how specificity can be achieved in the recognition of a ubiquitin-modified substrate.

PubMed: 28506460
DOI: 10.1016/j.molcel.2017.04.009

実験手法

SOLUTION NMR