title: Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase.
abstract: Legionella pneumophila is an opportunistic intracellular pathogen that causes sporadic and epidemic cases of Legionnaires' disease. Emerging data suggest that Legionella infection involves the subversion of host phosphoinositide (PI) metabolism. However, how this bacterium actively manipulates PI lipids to benefit its infection is still an enigma. Here, we report that the L. pneumophila virulence factor SidF is a phosphatidylinositol polyphosphate 3-phosphatase that specifically hydrolyzes the D3 phosphate of PI(3,4)P(2) and PI(3,4,5)P(3). This activity is necessary for anchoring of PI(4)P-binding effectors to bacterial phagosomes. Crystal structures of SidF and its complex with its substrate PI(3,4)P(2) reveal striking conformational rearrangement of residues at the catalytic site to form a cationic pocket that specifically accommodates the D4 phosphate group of the substrate. Thus, our findings unveil a unique Legionella PI phosphatase essential for the establishment of lipid identity of bacterial phagosomes.
authors.affiliation: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Fosheng
authors.initials: F
authors.lastname: Hsu
authors.forename: Wenhan
authors.initials: W
authors.lastname: Zhu
authors.forename: Lucy
authors.initials: L
authors.lastname: Brennan
authors.forename: Lili
authors.initials: L
authors.lastname: Tao
authors.forename: Zhao-Qing
authors.initials: ZQ
authors.lastname: Luo
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Mao
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray / Q000379:methods; D006868:Hydrolysis; D016952:Legionella pneumophila / Q000201:enzymology*; D008055:Lipids / Q000737:chemistry; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D008055:Lipids; D010716:Phosphatidylinositols; C089504:polyphosphoinositide phosphatase; D010744:Phosphoric Monoester Hydrolases