Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30.

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-A 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.
Mesh Terms:
Animals, Crystallography, X-Ray, DNA Mutational Analysis, Models, Molecular, Mutagenesis, Polyubiquitin, Protein Conformation, Ubiquitin-Specific Proteases, Zebrafish
Nat. Struct. Mol. Biol.
Date: Nov. 01, 2017
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