Identification and modelling of a PPM protein phosphatase fold in the Legionella pneumophila deAMPylase SidD

Area of Science:

• Microbiology
• Molecular Biology
• Structural Biology

Background:

• Legionella pneumophila is an intracellular bacterium that manipulates host cell processes.
• Vesicle transport is crucial for host cells and is targeted by L. pneumophila.
• Rab1 protein is modified by AMPylation, a reversible process regulated by bacterial effectors.

Purpose of the Study:

• To characterize the catalytic domain of the Legionella effector SidD.
• To determine the structural basis for SidD's deAMPylase activity.
• To identify potential new deAMPylases based on SidD's structural features.

Main Methods:

• Protein structure modeling based on sequence analysis.
• Identification of conserved catalytic domains.
• Comparative analysis of SidD's active site with known phosphatases.

Main Results:

• A complete PPM protein phosphatase fold was identified within the SidD catalytic domain.
• Structural modeling revealed unique insertions and deletions around the catalytic site.
• The SidD model suggests potential substrate-binding residues and highlights the absence of a general acid catalytic group.

Conclusions:

• SidD belongs to the PPM protein phosphatase family, explaining its deAMPylase function.
• The unique structural features of SidD's active site are responsible for its specific activity.
• This structural assignment provides a framework for discovering additional deAMPylases.