7oiy | pdb_00007oiy
Crystal structure of the ZUFSP family member Mug105
Structural highlights
FunctionMU105_SCHPO Deubiquitinase with endodeubiquitinase activity that preferentially cleaves 'Lys-48'-linked polyubiquitin chains (PubMed:29576528, PubMed:29476094). Shows only weak activity against 'Lys-63' and 'Lys-11'-linked chains (PubMed:29476094). Has a role in meiosis (PubMed:16303567).[1] [2] [3] Publication Abstract from PubMedEukaryotic 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. A structural basis for the diverse linkage specificities within the ZUFSP deubiquitinase family.,Hermanns T, Pichlo C, Baumann U, Hofmann K Nat Commun. 2022 Jan 20;13(1):401. doi: 10.1038/s41467-022-28049-6. PMID:35058438[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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