Identification and characterization of diverse OTU deubiquitinases in bacteria
Alexander F Schubert1, Justine V Nguyen2, Tyler G Franklin2
1Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Abstract:
Manipulation of host ubiquitin signaling is becoming an increasingly apparent evolutionary strategy among bacterial and viral pathogens. By removing host ubiquitin signals, for example, invading pathogens can inactivate immune response pathways and evade detection. The ovarian tumor (OTU) family of deubiquitinases regulates diverse ubiquitin signals in humans. Viral pathogens have also extensively co-opted the OTU fold to subvert host signaling, but the extent to which bacteria utilize the OTU fold was unknown. We have predicted and validated a set of OTU deubiquitinases encoded by several classes of pathogenic bacteria. Biochemical assays highlight the ubiquitin and polyubiquitin linkage specificities of these bacterial deubiquitinases. By determining the ubiquitin-bound structures of two examples, we demonstrate the novel strategies that have evolved to both thread an OTU fold and recognize a ubiquitin substrate. With these new examples, we perform the first cross-kingdom structural analysis of the OTU fold that highlights commonalities among distantly related OTU deubiquitinases.
Insights
Pathogenic bacteria utilize ovarian tumor (OTU) deubiquitinases to manipulate host ubiquitin signaling and evade immune detection. This study reveals novel bacterial OTU structures and functions, expanding our understanding of cross-kingdom deubiquitinase evolution.
Area of Science:
- Biochemistry
- Structural Biology
- Microbiology
Background:
- Pathogenic bacteria and viruses manipulate host ubiquitin signaling to evade immune responses.
- Ovarian tumor (OTU) deubiquitinases are key regulators of ubiquitin signaling in humans.
- The role of bacterial OTU deubiquitinases in pathogen evasion was previously unknown.
Purpose of the Study:
- To identify and characterize bacterial OTU deubiquitinases.
- To elucidate the structural basis and substrate specificities of bacterial OTU deubiquitinases.
- To perform a cross-kingdom structural comparison of OTU deubiquitinases.
Main Methods:
- Bioinformatic prediction of bacterial OTU deubiquitinases.
- Biochemical assays to determine deubiquitinase activity and specificity.
- X-ray crystallography to determine ubiquitin-bound structures.
Main Results:
- A set of OTU deubiquitinases encoded by pathogenic bacteria were identified and validated.
- Bacterial OTU deubiquitinases exhibit unique strategies for ubiquitin binding and cleavage.
- Structural analysis revealed conserved and divergent features of the OTU fold across kingdoms.
Conclusions:
- Bacterial pathogens employ OTU deubiquitinases as a strategy to subvert host immunity.
- The study provides novel structural insights into bacterial deubiquitinase mechanisms.
- This work establishes a foundation for understanding the evolution and function of OTU deubiquitinases across diverse organisms.
More Related Videos
10:25Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology
Published on: November 22, 2024
10:26Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
Published on: November 7, 2019
Related Concept Videos
The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
The Proteasome Structure
The proteasome is an...
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Cytoskeletal Proteins in Bacteria
