Study of Legionella Effector Domains Revealed Novel and Prevalent Phosphatidylinositol 3-Phosphate Binding Domains

• Published in: Infection and immunity Vol. 87; no. 6
• Main Authors: Nachmias, Nimrod, Zusman, Tal, Segal, Gil
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-06-2019
• Subjects: Amino Acid Sequence; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Legionella pneumophila - chemistry; Legionella pneumophila - genetics; Legionella pneumophila - metabolism; Molecular Pathogenesis; Phosphatidylinositol Phosphates - metabolism; Protein Binding; Protein Domains; Sequence Alignment; Icm/Dot; effectors; Legionella; PI3P-binding domains
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00153-19

and other
species replicate intracellularly using the Icm/Dot type IV secretion system. In
this system translocates >300 effectors into host cells and in the
genus thousands of effectors were identified, the function of most of which is unknown. Fourteen
effectors were previously shown to specifically bind phosphoinositides (PIs) using dedicated domains. We found that PI-binding domains of effectors are usually not homologous to one another; they are relatively small and located at the effectors' C termini. We used the previously identified
effector domains (LEDs) with unknown function and the above characteristics of effector PI-binding domains to discover novel PI-binding LEDs. We identified three predicted PI-binding LEDs that are present in 14 
effectors and in >200 effectors in the
genus. Using an
protein-lipid overlay assay, we found that 11 of these
effectors specifically bind phosphatidylinositol 3-phosphate (PI3P), almost doubling the number of
effectors known to bind PIs. Further, we identified in each of these newly discovered PI3P-binding LEDs conserved, mainly positively charged, amino acids that are essential for PI3P binding. Our results indicate that
effectors harbor unique domains, shared by many effectors, which directly mediate PI3P binding.