The structural basis for deubiquitination by the fingerless USP-type effector TssM
Thomas Hermanns1, Matthias Uthoff2, Ulrich Baumann2
1Institute for Genetics, University of Cologne, Cologne, Germany t.hermanns@uni-koeln.de.
Life Science Alliance
|January 3, 2024
Summary
Intracellular bacteria use deubiquitinase (DUB) effectors to evade host defenses. Researchers discovered Burkholderia TssM, a unique USP-class DUB, with a novel "Littlefinger" loop for ubiquitin recognition.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Intracellular bacteria face ubiquitin-mediated autophagy, a host defense mechanism.
- Bacterial deubiquitinase (DUB) effectors are crucial for evading this process.
- Most bacterial DUBs are OTU or CE-clan, but Burkholderia species possess the USP-class TssM effector.
Purpose of the Study:
- To elucidate the structure and function of the TssM effector from Burkholderia pseudomallei and Burkholderia mallei.
- To understand the unique ubiquitin-recognition mechanism of TssM, a USP-class bacterial DUB.
Main Methods:
- X-ray crystallography was used to determine the structures of isolated TssM and its complex with ubiquitin.
- Structural analysis focused on identifying key domains and functional regions involved in DUB activity and localization.
Main Results:
- TssM lacks the canonical 'Fingers' subdomain typical of eukaryotic USP enzymes.
- A novel 'Littlefinger' loop was identified, mediating distinct ubiquitin interface recognition.
- An N-terminal immunoglobulin-fold domain capable of forming a strand-exchange dimer was observed, potentially involved in bacterial surface localization.
Conclusions:
- TssM represents a unique bacterial USP-class deubiquitinase with a divergent ubiquitin-binding strategy.
- The novel 'Littlefinger' loop and immunoglobulin-fold domain highlight evolutionary adaptations in bacterial effector proteins.
- These findings provide insights into bacterial strategies for subverting host immunity and potential targets for therapeutic intervention.
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