Structural Basis of Lipid Targeting and Destruction by the Type V Secretion System of Pseudomonas aeruginosa

The type V secretion system is a macromolecular machine employed by a number of bacteria to secrete virulence factors into the environment. The human pathogen Pseudomonas aeruginosa employs the newly described type Vd secretion system to secrete a soluble variant of PIpD, a lipase of the patatin-like family synthesized as a single macromolecule that also carries a polypeptide transport-associated domain and a 16-stranded beta-barrel. Here we report the crystal structure of the secreted form of PIpD in its biologically active state. PIpD displays a classical lipase alpha/beta hydrolase fold with a catalytic site located within a highly hydrophobic channel that entraps a lipidic molecule. The active site is covered by a flexible lid, as in other lipases, indicating that this region in PlpD must modify its conformation in order for catalysis at the water lipid interface to occur. PlpD displays phospholipase A(1) activity and is able to recognize a number of phosphatidylinositols and other phosphatidyl analogs. PIpD is the first example of an active phospholipase secreted through the type V secretion system, for which there are more than 200 homologs, revealing details of the lipid destruction arsenal expressed by P. aeruginosa in order to establish infection. (C) 2016 Elsevier Ltd. All rights reserved.