4JZA

Crystal structure of a Legionella phosphoinositide phosphatase: insights into lipid metabolism in pathogen host interaction

Summary for 4JZA

• Entry DOI: 10.2210/pdb4jza/pdb
• Related: 4FYE 4FYF 4FYG
• Descriptor: Uncharacterized protein (2 entities in total)
• Functional Keywords: alpha beta fold, phosphatase, hydrolase
• Biological source: Legionella longbeachae NSW150
• Total number of polymer chains: 2
• Total formula weight: 190099.98

Authors

Toulabi, L.,Wu, X.,Cheng, Y.,Mao, Y. (deposition date: 2013-04-02, release date: 2013-07-17, Last modification date: 2024-10-30)

Primary citation

Toulabi, L.,Wu, X.,Cheng, Y.,Mao, Y.
Identification and structural characterization of a legionella phosphoinositide phosphatase.
J.Biol.Chem., 288:24518-24527, 2013

PubMed Abstract: Bacterial pathogen Legionella pneumophila is the causative agent of Legionnaires' disease, which is associated with intracellular replication of the bacteria in macrophages of human innate immune system. Recent studies indicate that pathogenic bacteria can subvert host cell phosphoinositide (PI) metabolism by translocated virulence effectors. However, in which manner Legionella actively exploits PI lipids to benefit its infection is not well characterized. Here we report that L. pneumophila encodes an effector protein, named SidP, that functions as a PI-3-phosphatase specifically hydrolyzing PI(3)P and PI(3,5)P2 in vitro. This activity of SidP rescues the growth phenotype of a yeast strain defective in PI(3)P phosphatase activity. Crystal structure of SidP orthologue from Legionella longbeachae reveals that this unique PI-3-phosphatase is composed of three distinct domains: a large catalytic domain, an appendage domain that is inserted into the N-terminal portion of the catalytic domain, and a C-terminal α-helical domain. SidP has a small catalytic pocket that presumably provides substrate specificity by limiting the accessibility of bulky PIs with multiple phosphate groups. Together, our identification of a unique family of Legionella PI phosphatases highlights a common scheme of exploiting host PI lipids in many intracellular bacterial pathogen infections.

PubMed: 23843460
DOI: 10.1074/jbc.M113.474239

Experimental method

X-RAY DIFFRACTION (2.584 Å)