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Updated: Jun 30, 2025

Purification of Pathogen Vacuoles from Legionella-infected Phagocytes
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Legionella metaeffector MavL reverses ubiquitin ADP-ribosylation via a conserved arginine-specific macrodomain

Zhengrui Zhang1, Jiaqi Fu2, Johannes Gregor Matthias Rack3,4

  • 1Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.

Nature Communications
|March 20, 2024
PubMed

Insights

Legionella effector MavL reverses ubiquitin ADP-ribosylation, regulating pathogen-induced ubiquitination. This study reveals novel macrodomain enzymes, including eukaryotic ones, involved in ADP-ribosylation and de-ADP-ribosylation processes.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • ADP-ribosylation is a reversible post-translational modification crucial for cellular functions.
  • Macrodomain enzymes are key players in removing ADP-ribosylation marks.
  • Legionella pneumophila utilizes the SidE effector family for atypical ubiquitination, involving arginine ADP-ribosylation.

Purpose of the Study:

  • To investigate the role of Legionella macrodomain effector MavL in regulating SidE-mediated ubiquitination.
  • To elucidate the structural basis of MavL's ADP-ribosylhydrolase activity.
  • To identify and characterize novel macrodomain enzymes with similar functions.

Main Methods:

  • Crystal structure determination of ADP-ribose-bound MavL.
  • Biochemical assays to assess enzymatic activity and substrate specificity.
  • Structural analysis of DUF4804 family proteins and eukaryotic homologs.

Main Results:

  • MavL reverses arginine ADP-ribosylation on ubiquitin, acting as a (ADP-ribosyl)hydrolase.
  • The crystal structure of MavL reveals its mechanism for recognizing and removing ADP-ribose.
  • DUF4804 proteins, including eukaryotic homologs from Drosophila melanogaster, represent a new class of macrodomain enzymes with arginine specificity.

Conclusions:

  • MavL provides a regulatory mechanism for SidE-catalyzed ubiquitination, preventing potential detrimental effects.
  • The study expands the known repertoire of macrodomain enzymes and their functions in de-ADP-ribosylation.
  • Structural insights into MavL and DUF4804 enzymes offer a deeper understanding of ADP-ribosylation regulation.

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