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Updated: May 19, 2026
10:58
PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions
Published on: July 27, 2017
Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase.
Fosheng Hsu1, Wenhan Zhu, Lucy Brennan
1Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
Summary
Legionella pneumophila uses the virulence factor SidF, a novel phosphatase, to manipulate host phosphoinositide metabolism. This action is crucial for anchoring effector proteins to bacterial phagosomes during infection.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Legionella pneumophila causes Legionnaires' disease by subverting host cell processes.
- Host phosphoinositide (PI) metabolism is implicated in Legionella infection.
- The precise mechanisms of PI lipid manipulation by Legionella remain unclear.
Purpose of the Study:
- To investigate the role of Legionella virulence factors in manipulating host PI metabolism.
- To identify the specific PI phosphatase activity of the L. pneumophila effector SidF.
- To elucidate the structural basis for SidF's enzymatic function.
Main Methods:
- Biochemical assays to determine SidF's phosphatase activity.
- Analysis of PI lipid hydrolysis specificity.
- X-ray crystallography to determine SidF structure and substrate complex.
Main Results:
- SidF functions as a phosphatidylinositol polyphosphate 3-phosphatase, hydrolyzing D3 phosphates of PI(3,4)P(2) and PI(3,4,5)P(3).
- This activity is essential for the recruitment of PI(4)P-binding effectors to Legionella-containing vacuoles.
- Structural analysis revealed a unique catalytic site accommodating the substrate's D4 phosphate.
Conclusions:
- SidF is a novel Legionella PI phosphatase critical for establishing phagosome lipid identity.
- The findings provide insights into host-pathogen interactions and PI lipid signaling.
- SidF represents a potential target for therapeutic intervention against Legionnaires' disease.
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