4AYC

RNF8 RING domain structure

4AYC の概要

• エントリーDOI: 10.2210/pdb4ayc/pdb
• 関連するPDBエントリー: 2CSW
• 分子名称: E3 UBIQUITIN-PROTEIN LIGASE RNF8, SULFATE ION, N,N-BIS(3-D-GLUCONAMIDOPROPYL)DEOXYCHOLAMIDE, ... (8 entities in total)
• 機能のキーワード: ligase, dna damage, k63 chains
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus: O76064 O76064
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34261.59

構造登録者

Mattiroli, F.,Vissers, J.H.A.,Van Dijk, W.J.,Ikpa, P.,Citterio, E.,Vermeulen, W.,Marteijn, J.A.,Sixma, T.K. (登録日: 2012-06-20, 公開日: 2012-09-26, 最終更新日: 2024-11-13)

主引用文献

Mattiroli, F.,Vissers, J.H.A.,Van Dijk, W.J.,Ikpa, P.,Citterio, E.,Vermeulen, W.,Marteijn, J.A.,Sixma, T.K.
Rnf168 Ubiquitinates K13-15 on H2A/H2Ax to Drive DNA Damage Signaling
Cell(Cambridge,Mass.), 150:1182-, 2012

PubMed Abstract: Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination. This suggests that RNF8 initiates H2A/H2AX ubiquitination with K63-linked ubiquitin chains and RNF168 extends them. Here, we show that RNF8 is inactive toward nucleosomal H2A, whereas RNF168 catalyzes the monoubiquitination of the histones specifically on K13-15. Structure-based mutagenesis of RNF8 and RNF168 RING domains shows that a charged residue determines whether nucleosomal proteins are recognized. We find that K63 ubiquitin chains are conjugated to RNF168-dependent H2A/H2AX monoubiquitination at K13-15 and not on K118-119. Using a mutant of RNF168 unable to target histones but still catalyzing ubiquitin chains at DSBs, we show that ubiquitin chains per se are insufficient for signaling, but RNF168 target ubiquitination is required for DDR.

PubMed: 22980979
DOI: 10.1016/J.CELL.2012.08.005

実験手法

X-RAY DIFFRACTION (1.9 Å)