5GG4

Crystal structure of USP7 with RNF169 peptide

5GG4 の概要

• エントリーDOI: 10.2210/pdb5gg4/pdb
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 7, Peptide from E3 ubiquitin-protein ligase RNF169 (2 entities in total)
• 機能のキーワード: hydrolase/ligase, hydrolase-ligase complex
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : Q93009; Nucleus, nucleoplasm : Q8NCN4
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 162104.17

構造登録者

Jiang, Y.,Gong, Q. (登録日: 2016-06-15, 公開日: 2017-03-22, 最終更新日: 2023-11-08)

主引用文献

An, L.,Jiang, Y.,Ng, H.H.,Man, E.P.,Chen, J.,Khoo, U.S.,Gong, Q.,Huen, M.S.
Dual-utility NLS drives RNF169-dependent DNA damage responses.
Proc. Natl. Acad. Sci. U.S.A., 114:E2872-E2881, 2017

PubMed Abstract: Loading of p53-binding protein 1 (53BP1) and receptor-associated protein 80 (RAP80) at DNA double-strand breaks (DSBs) drives cell cycle checkpoint activation but is counterproductive to high-fidelity DNA repair. ring finger protein 169 (RNF169) maintains the balance by limiting the deposition of DNA damage mediator proteins at the damaged chromatin. We report here that this attribute is accomplished, in part, by a predicted nuclear localization signal (NLS) that not only shuttles RNF169 into the nucleus but also promotes its stability by mediating a direct interaction with the ubiquitin-specific protease USP7. Guided by the crystal structure of USP7 in complex with the RNF169 NLS, we uncoupled USP7 binding from its nuclear import function and showed that perturbing the USP7-RNF169 complex destabilized RNF169, compromised high-fidelity DSB repair, and hypersensitized cells to poly (ADP-ribose) polymerase inhibition. Finally, expression of USP7 and RNF169 positively correlated in breast cancer specimens. Collectively, our findings uncover an NLS-mediated bipartite mechanism that supports the nuclear function of a DSB response protein.

PubMed: 28325877
DOI: 10.1073/pnas.1616602114

実験手法

X-RAY DIFFRACTION (3.11 Å)