3L11

Crystal Structure of the Ring Domain of RNF168

3L11 の概要

• エントリーDOI: 10.2210/pdb3l11/pdb
• 分子名称: E3 ubiquitin-protein ligase RNF168, ZINC ION, MALONATE ION, ... (4 entities in total)
• 機能のキーワード: e3 ligase, ring domain, dna damage, chromatin regulator, chromosomal protein, dna repair, ligase, metal-binding, nucleus, phosphoprotein, ubl conjugation pathway, zinc-finger, structural genomics, structural genomics consortium, sgc
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q8IYW5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13466.16

構造登録者

Neculai, D.,Yermekbayeva, L.,Crombet, L.,Weigelt, J.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (登録日: 2009-12-10, 公開日: 2010-01-19, 最終更新日: 2023-09-06)

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 (2.12 Å)