5OHK

Crystal structure of USP30 in covalent complex with ubiquitin propargylamide (high resolution)

Summary for 5OHK

• Entry DOI: 10.2210/pdb5ohk/pdb
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 30,Ubiquitin carboxyl-terminal hydrolase 30,Ubiquitin carboxyl-terminal hydrolase 30, Polyubiquitin-B, ZINC ION, ... (5 entities in total)
• Functional Keywords: deubiquitinase, dub, ubiquitin, usp, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Mitochondrion outer membrane : Q70CQ3; Ubiquitin: Cytoplasm : P0CG47
• Total number of polymer chains: 2
• Total formula weight: 47150.78

Authors

Gersch, M.,Komander, D. (deposition date: 2017-07-17, release date: 2017-09-20, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.34 Å)