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.

The EMBO Journal
|June 23, 2020
PubMed

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.

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