Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling

Area of Science:

• Microbiology
• Biochemistry
• Molecular Biology

Background:

• AMPylation is a post-translational modification involving AMP addition to protein side chains.
• Legionella pneumophila utilizes effector proteins to manipulate host cells during infection.

Purpose of the Study:

• To investigate the AMPylase activity of Legionella pneumophila effector protein LnaB.
• To elucidate the mechanism and structural basis of LnaB's unique phosphoryl AMPylation.
• To understand LnaB's role in bacterial pathogenesis and host cell signaling.

Main Methods:

• Biochemical assays to determine LnaB's enzymatic activity.
• Structural studies (e.g., X-ray crystallography) to resolve LnaB's structure and mechanism.
• In vitro and in vivo experiments to assess LnaB's effect on host proteins and signaling pathways.

Main Results:

• LnaB exhibits novel AMPylase activity towards phosphoribose on ubiquitinated proteins (PR^R42-Ub).
• LnaB AMPylates phosphorylated tyrosine residues in Src family kinases, inhibiting host signaling.
• LnaB represents a distinct family of AMPylases found in numerous bacterial pathogens.

Conclusions:

• LnaB employs a unique mechanism to AMPylate phosphoribose and protein tyrosine residues.
• This AMPylation activity serves to dampen host cell phosphorylation signaling during infection.
• LnaB and its homologues represent a significant class of bacterial virulence factors with potential therapeutic implications.