7OJE

Crystal structure of the covalent complex between Tribolium castaneum deubiquitinase ZUP and Ubiquitin-PA

Summary for 7OJE

• Entry DOI: 10.2210/pdb7oje/pdb
• Descriptor: Lys-63-specific deubiquitinase ZUFSP, Polyubiquitin-B, CITRIC ACID, ... (7 entities in total)
• Functional Keywords: zufsp, deubiquitinase, tribolium castaneum, red flour beetle, cysteine peptidase, ubiquitin, ubiquitin-propargylamide, hydrolase
• Biological source: Tribolium castaneum (Red flour beetle); More
• Total number of polymer chains: 4
• Total formula weight: 101864.51

Authors

Pichlo, C.,Hermanns, T.,Hofmann, K.,Baumann, U. (deposition date: 2021-05-14, release date: 2022-02-02, Last modification date: 2024-11-06)

Primary citation

Hermanns, T.,Pichlo, C.,Baumann, U.,Hofmann, K.
A structural basis for the diverse linkage specificities within the ZUFSP deubiquitinase family.
Nat Commun, 13:401-401, 2022

PubMed Abstract: Eukaryotic deubiquitinases are important regulators of ubiquitin signaling and can be subdivided into several structurally distinct classes. The ZUFSP family, with ZUP1 as its sole human member, has a modular architecture with a core catalytic domain highly active against the ubiquitin-derived peptide RLRGG, but not against ubiquitin itself. Ubiquitin recognition is conferred by additional non-catalytic domains, making full-length ZUP1 active against long K63-linked chains. However, non-mammalian ZUFSP family members contain different ubiquitin-binding domains in their N-terminal regions, despite their high conservation within the catalytic domain. Here, by working with representative ZUFSP family members from insects, fungi and plants, we show that different N-terminal domains are associated with different linkage preferences. Biochemical and structural studies suggest that the acquisition of two family-specific proximal domains have changed the default K48 preference of the ZUFSP family to the K63 preference observed in ZUP1 and its insect homolog. Additional N-terminal zinc finger domains promote chain cleavage without changing linkage-specificity.

PubMed: 35058438
DOI: 10.1038/s41467-022-28049-6

Experimental method

X-RAY DIFFRACTION (2.05 Å)