3A1Q

Crystal structure of the mouse RAP80 UIMs in complex with Lys63-linked di-ubiquitin

3A1Q の概要

• エントリーDOI: 10.2210/pdb3a1q/pdb
• 分子名称: Ubiquitin, Ubiquitin interaction motif-containing protein 1, ... (4 entities in total)
• 機能のキーワード: protein complex, cytoplasm, nucleus, phosphoprotein, ubl conjugation, transcription regulation, gene regulation-signaling protein complex, gene regulation/signaling protein
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Nucleus (By similarity): Q5U5Q9
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 44754.57

構造登録者

Sato, Y.,Yoshikawa, A.,Mimura, H.,Yamashita, M.,Yamagata, A.,Fukai, S. (登録日: 2009-04-21, 公開日: 2009-07-21, 最終更新日: 2023-11-01)

主引用文献

Sato, Y.,Yoshikawa, A.,Mimura, H.,Yamashita, M.,Yamagata, A.,Fukai, S.
Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80
Embo J., 28:2461-2468, 2009

PubMed Abstract: RAP80 has a key role in the recruitment of the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA-damage foci for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs (UIMs). Here, we report the crystal structure of the RAP80 tandem UIMs (RAP80-UIM1-UIM2) in complex with Lys 63-linked di-ubiquitin at 2.2 A resolution. The two UIMs, UIM1 and UIM2, and the alpha-helical inter-UIM region together form a continuous 60 A-long alpha-helix. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties, respectively. Both UIM1 and UIM2 of RAP80 recognize an Ile 44-centered hydrophobic patch on ubiquitin but neither UIM interacts with the Lys 63-linked isopeptide bond. Our structure suggests that the inter-UIM region forms a 12 A-long alpha-helix that ensures that the UIMs are arranged to enable specific binding of Lys 63-linked di-ubiquitin. This was confirmed by pull-down analyses using RAP80-UIM1-UIM2 mutants of various length inter-UIM regions. Further, we show that the Epsin1 tandem UIM, which has an inter-UIM region similar to that of RAP80-UIM1-UIM2, also selectively binds Lys 63-linked di-ubiquitin.

PubMed: 19536136
DOI: 10.1038/emboj.2009.160

実験手法

X-RAY DIFFRACTION (2.2 Å)