PUBLICATION
Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30
- Authors
- Sato, Y., Okatsu, K., Saeki, Y., Yamano, K., Matsuda, N., Kaiho, A., Yamagata, A., Goto-Ito, S., Ishikawa, M., Hashimoto, Y., Tanaka, K., Fukai, S.
- ID
- ZDB-PUB-170926-3
- Date
- 2017
- Source
- Nature structural & molecular biology 24(11): 911-919 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Crystallography, X-Ray
- DNA Mutational Analysis
- Models, Molecular
- Mutagenesis
- Polyubiquitin/metabolism*
- Protein Conformation
- Ubiquitin-Specific Proteases/chemistry*
- Ubiquitin-Specific Proteases/genetics
- Ubiquitin-Specific Proteases/metabolism*
- Zebrafish
- PubMed
- 28945247 Full text @ Nat. Struct. Mol. Biol.
Citation
Sato, Y., Okatsu, K., Saeki, Y., Yamano, K., Matsuda, N., Kaiho, A., Yamagata, A., Goto-Ito, S., Ishikawa, M., Hashimoto, Y., Tanaka, K., Fukai, S. (2017) Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30. Nature structural & molecular biology. 24(11):911-919.
Abstract
Parkin ubiquitin (Ub) ligase (also known as PARK2) ubiquitinates damaged mitochondria for their clearance and quality control. USP30 deubiquitinase opposes parkin-mediated Ub-chain formation on mitochondria by preferentially cleaving Lys6-linked Ub chains. Here, we report the crystal structure of zebrafish USP30 in complex with a Lys6-linked diubiquitin (diUb or Ub2) at 1.87-Å resolution. The distal Ub-recognition mechanism of USP30 is similar to those of other USP family members, whereas Phe4 and Thr12 of the proximal Ub are recognized by a USP30-specific surface. Structure-based mutagenesis showed that the interface with the proximal Ub is critical for the specific cleavage of Lys6-linked Ub chains, together with the noncanonical catalytic triad composed of Cys-His-Ser. The structural findings presented here reveal a mechanism for Lys6-linkage-specific deubiquitination.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping