4ORH

Crystal structure of RNF8 bound to the UBC13/MMS2 heterodimer

「4EPO」から置き換えられました

4ORH の概要

• エントリーDOI: 10.2210/pdb4orh/pdb
• 分子名称: Ubiquitin-conjugating enzyme E2 variant 2, Ubiquitin-conjugating enzyme E2 N, E3 ubiquitin-protein ligase RNF8, ... (4 entities in total)
• 機能のキーワード: coiled-coil, e3 ubiquitin ligase, ubiquitin, protein binding-ligase, protein binding-ligase complex, protein binding/ligase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : P61088 O76064
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 194211.17

構造登録者

Campbell, S.J.,Edwards, R.A.,Glover, J.N.M. (登録日: 2014-02-11, 公開日: 2014-02-26, 最終更新日: 2024-02-28)

主引用文献

Campbell, S.J.,Edwards, R.A.,Leung, C.C.,Neculai, D.,Hodge, C.D.,Dhe-Paganon, S.,Glover, J.N.
Molecular insights into the function of RING finger (RNF)-containing proteins hRNF8 and hRNF168 in Ubc13/Mms2-dependent ubiquitylation.
J.Biol.Chem., 287:23900-23910, 2012

PubMed Abstract: The repair of DNA double strand breaks by homologous recombination relies on the unique topology of the chains formed by Lys-63 ubiquitylation of chromatin to recruit repair factors such as breast cancer 1 (BRCA1) to sites of DNA damage. The human RING finger (RNF) E3 ubiquitin ligases, RNF8 and RNF168, with the E2 ubiquitin-conjugating complex Ubc13/Mms2, perform the majority of Lys-63 ubiquitylation in homologous recombination. Here, we show that RNF8 dimerizes and binds to Ubc13/Mms2, thereby stimulating formation of Lys-63 ubiquitin chains, whereas the related RNF168 RING domain is a monomer and does not catalyze Lys-63 polyubiquitylation. The crystal structure of the RNF8/Ubc13/Mms2 ternary complex reveals the structural basis for the interaction between Ubc13 and the RNF8 RING and that an extended RNF8 coiled-coil is responsible for its dimerization. Mutations that disrupt the RNF8/Ubc13 binding surfaces, or that truncate the RNF8 coiled-coil, reduce RNF8-catalyzed ubiquitylation. These findings support the hypothesis that RNF8 is responsible for the initiation of Lys-63-linked ubiquitylation in the DNA damage response, which is subsequently amplified by RNF168.

PubMed: 22589545
DOI: 10.1074/jbc.M112.359653

実験手法

X-RAY DIFFRACTION (4.802 Å)