6EI1

Crystal structure of the covalent complex between deubiquitinase ZUFSP (ZUP1) and Ubiquitin-PA

Summary for 6EI1

• Entry DOI: 10.2210/pdb6ei1/pdb
• Descriptor: Zinc finger with UFM1-specific peptidase domain protein, Polyubiquitin-B, prop-2-en-1-amine, ... (6 entities in total)
• Functional Keywords: k63, ubiquitin, deubiquitinase, cysteine peptidase, hydrolase, zup1
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 48506.36

Authors

Pichlo, C.,Baumann, U.,Hofmann, K.,Hermanns, T. (deposition date: 2017-09-16, release date: 2018-03-07, Last modification date: 2025-04-09)

Primary citation

Hermanns, T.,Pichlo, C.,Woiwode, I.,Klopffleisch, K.,Witting, K.F.,Ovaa, H.,Baumann, U.,Hofmann, K.
A family of unconventional deubiquitinases with modular chain specificity determinants.
Nat Commun, 9:799-799, 2018

PubMed 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.

PubMed: 29476094
DOI: 10.1038/s41467-018-03148-5

Experimental method

X-RAY DIFFRACTION (1.732 Å)