6A6I

Crystal structure of the winged-helix domain of Cockayne syndrome group B protein in complex with ubiquitin

6A6I の概要

• エントリーDOI: 10.2210/pdb6a6i/pdb
• 分子名称: Excision repair cross-complementing rodent repair deficiency, complementation group 6 variant, Polyubiquitin-B, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: dna repair, helicase, ubiquitin, molecular signaling, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 79315.13

構造登録者

Takahashi, T.S.,Sato, Y.,Fukai, S. (登録日: 2018-06-28, 公開日: 2019-02-13, 最終更新日: 2024-11-06)

主引用文献

Takahashi, T.S.,Sato, Y.,Yamagata, A.,Goto-Ito, S.,Saijo, M.,Fukai, S.
Structural basis of ubiquitin recognition by the winged-helix domain of Cockayne syndrome group B protein.
Nucleic Acids Res., 47:3784-3794, 2019

PubMed Abstract: Cockayne syndrome group B (CSB, also known as ERCC6) protein is involved in many DNA repair processes and essential for transcription-coupled repair (TCR). The central region of CSB has the helicase motif, whereas the C-terminal region contains important regulatory elements for repair of UV- and oxidative stress-induced damages and double-strand breaks (DSBs). A previous study suggested that a small part (∼30 residues) within this region was responsible for binding to ubiquitin (Ub). Here, we show that the Ub-binding of CSB requires a larger part of CSB, which was previously identified as a winged-helix domain (WHD) and is involved in the recruitment of CSB to DSBs. We also present the crystal structure of CSB WHD in complex with Ub. CSB WHD folds as a single globular domain, defining a class of Ub-binding domains (UBDs) different from 23 UBD classes identified so far. The second α-helix and C-terminal extremity of CSB WHD interact with Ub. Together with structure-guided mutational analysis, we identified the residues critical for the binding to Ub. CSB mutants defective in the Ub binding reduced repair of UV-induced damage. This study supports the notion that DSB repair and TCR may be associated with the Ub-binding of CSB.

PubMed: 30753618
DOI: 10.1093/nar/gkz081

実験手法

X-RAY DIFFRACTION (2.6 Å)