A family of unconventional deubiquitinases with modular chain specificity determinants

Thomas Hermanns, Christian Pichlo, Ilka Woiwode, Karsten Klopffleisch, Katharina F. Witting, Huib Ovaa, Ulrich Baumann and Kay Hofmann ()
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Thomas Hermanns: University of Cologne
Christian Pichlo: University of Cologne
Ilka Woiwode: University of Cologne
Karsten Klopffleisch: University of Cologne
Katharina F. Witting: Leiden University Medical Center
Huib Ovaa: Leiden University Medical Center
Ulrich Baumann: University of Cologne
Kay Hofmann: University of Cologne

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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 ZUFSP (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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03148-5

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DOI: 10.1038/s41467-018-03148-5

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