5OHP

Crystal structure of USP30 (C77A) in complex with Lys6-linked diubiquitin

5OHP の概要

• エントリーDOI: 10.2210/pdb5ohp/pdb
• 関連するPDBエントリー: 5OHK
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 30, Polyubiquitin-B, ZINC ION, ... (4 entities in total)
• 機能のキーワード: dub, ubiquitin, usp, k6, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 55656.43

構造登録者

Gersch, M.,Komander, D. (登録日: 2017-07-17, 公開日: 2017-09-20, 最終更新日: 2024-01-17)

主引用文献

Gersch, M.,Gladkova, C.,Schubert, A.F.,Michel, M.A.,Maslen, S.,Komander, D.
Mechanism and regulation of the Lys6-selective deubiquitinase USP30.
Nat. Struct. Mol. Biol., 24:920-930, 2017

PubMed Abstract: Damaged mitochondria undergo mitophagy, a specialized form of autophagy that is initiated by the protein kinase PINK1 and the ubiquitin E3 ligase Parkin. Ubiquitin-specific protease USP30 antagonizes Parkin-mediated ubiquitination events on mitochondria and is a key negative regulator of mitophagy. Parkin and USP30 both show a preference for assembly or disassembly, respectively, of Lys6-linked polyubiquitin, a chain type that has not been well studied. Here we report crystal structures of human USP30 bound to monoubiquitin and Lys6-linked diubiquitin, which explain how USP30 achieves Lys6-linkage preference through unique ubiquitin binding interfaces. We assess the interplay between USP30, PINK1 and Parkin and show that distally phosphorylated ubiquitin chains impair USP30 activity. Lys6-linkage-specific affimers identify numerous mitochondrial substrates for this modification, and we show that USP30 regulates Lys6-polyubiquitinated TOM20. Our work provides insights into the architecture, activity and regulation of USP30, which will aid drug design against this and related enzymes.

PubMed: 28945249
DOI: 10.1038/nsmb.3475

実験手法

X-RAY DIFFRACTION (2.8 Å)