Download MendeleyA family of bacterial Josephin-like deubiquitinases with an irreversible cleavage mode.
Hermanns, T., Kolek, S., Uthoff, M., de Heiden, R.A., Mulder, M.P.C., Baumann, U., Hofmann, K.(2025) Mol Cell 85: 1202-1215.e5
- PubMed: 40037356
- DOI: https://doi.org/10.1016/j.molcel.2025.02.002
- Primary Citation of Related Structures:
9F5T, 9FN4, 9FPA, 9G7G - PubMed Abstract:
Many intracellular bacteria secrete deubiquitinase (DUB) effectors into eukaryotic host cells to keep the bacterial surface or the enclosing vesicle membrane free of ubiquitin marks. This study describes a family of DUBs from several bacterial genera, including Simkania, Parachlamydia, Burkholderia, and Pigmentiphaga, which is structurally related to eukaryotic Josephin-type DUBs but contains members that catalyze a unique destructive substrate deubiquitination. These ubiquitin C-terminal clippases (UCCs) cleave ubiquitin before the C-terminal diGly motif, thereby truncating the modifier and leaving a remnant on the substrate. By comparing the crystal structures of substrate-bound clippases and a closely related conventional DUB, we identified the factors causing this shift and found them to be conserved in other clippases, including one highly specific for M1-linked ubiquitin chains. This enzyme class has great potential to serve as tools for studying the ubiquitin system, particularly aspects involving branched chains.
Organizational Affiliation:
Institute for Genetics, University of Cologne, Zülpicher Straße 47a, 50674 Cologne, Germany.
