A family of unconventional deubiquitinases with modular chain specificity determinants.
Deubiquitinating enzymes (DUBs) regulate ubiquitin signaling by trimming ubiquitin chains or removing ubiquitin from modified substrates. Similar activities exist for ubiquitin-related modifiers, although the enzymes involved are usually not related. Here, we report human ZUFSPÂ (also known as ZUP1 and C6orf113) and fission yeast Mug105 as founding members of a DUB ... family different from the six known DUB classes. The crystal structure of human ZUFSP in covalent complex with propargylated ubiquitin shows that the DUB family shares a fold with UFM1- and Atg8-specific proteases, but uses a different active site more similar to canonical DUB enzymes. ZUFSP family members differ widely in linkage specificity through differential use of modular ubiquitin-binding domains (UBDs). While the minimalistic Mug105 prefers K48 chains, ZUFSP uses multiple UBDs for its K63-specific endo-DUB activity. K63 specificity, localization, and protein interaction network suggest a role for ZUFSP in DNA damage response.
Mesh Terms:
Catalytic Domain, Deubiquitinating Enzymes, Humans, Multigene Family, Protein Binding, Protein Domains, Schizosaccharomyces, Substrate Specificity, Ubiquitin
Catalytic Domain, Deubiquitinating Enzymes, Humans, Multigene Family, Protein Binding, Protein Domains, Schizosaccharomyces, Substrate Specificity, Ubiquitin
Nat Commun
Date: Dec. 23, 2017
PubMed ID: 29476094
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