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Updated: May 3, 2026

Applying Live Cell Imaging and Cryo-Electron Tomography to Resolve Spatiotemporal Features of the Legionella pneumophila Dot/Icm Secretion System
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Structural basis for PI(4)P-specific membrane recruitment of the Legionella pneumophila effector DrrA/SidM

Claudia M Del Campo1, Ashwini K Mishra1, Yu-Hsiu Wang2

  • 1Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Structure (London, England : 1993)
|February 18, 2014
PubMed

Insights

The Legionella pneumophila effector DrrA uses its P4M domain to specifically bind phosphatidylinositol 4-phosphate (PI(4)P). This interaction is crucial for recruiting DrrA to the vacuole membrane, enabling pathogen virulence.

Area of Science:

  • Microbiology
  • Structural Biology
  • Cell Biology

Background:

  • Phosphatidylinositol 4-phosphate (PI(4)P) is vital for Golgi trafficking.
  • Pathogens like Legionella pneumophila manipulate host cell membranes.
  • The structural basis for PI(4)P-dependent membrane recruitment by effectors is poorly understood.

Purpose of the Study:

  • To elucidate the structural mechanism of DrrA's P4M domain binding to PI(4)P.
  • To investigate the molecular determinants of phosphoinositide recognition and membrane targeting by DrrA.

Main Methods:

  • X-ray crystallography to determine the structure of the DrrA P4M domain in complex with PI(4)P.
  • Biochemical and biophysical assays to analyze phosphoinositide binding and membrane association.

Main Results:

  • The crystal structure reveals a deep binding pocket for the PI(4)P headgroup, involving specific polar and basic residues.
  • An adjacent hydrophobic helical element interacts with PI(4)P acyl chains and promotes membrane insertion.
  • DrrA exhibits high-affinity and specific binding to PI(4)P, driving membrane recruitment.

Conclusions:

  • A detailed structural mechanism for PI(4)P-dependent membrane targeting by DrrA has been established.
  • Understanding this interaction provides insights into pathogen manipulation of host membranes.
  • This work clarifies the role of phosphoinositides in effector-mediated membrane recruitment.

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