6A6I

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

Summary for 6A6I

• Entry DOI: 10.2210/pdb6a6i/pdb
• Descriptor: Excision repair cross-complementing rodent repair deficiency, complementation group 6 variant, Polyubiquitin-B, GLYCEROL, ... (6 entities in total)
• Functional Keywords: dna repair, helicase, ubiquitin, molecular signaling, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 79315.13

Authors

Takahashi, T.S.,Sato, Y.,Fukai, S. (deposition date: 2018-06-28, release date: 2019-02-13, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)