Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA

Abstract

PldA, a phospholipase D (PLD) effector, catalyzes hydrolysis of the phosphodiester bonds of glycerophospholipids—the main component of cell membranes—and assists the invasion of the opportunistic pathogen Pseudomonas aeruginosa. In this work, the authors report three intermediate structures of PldA by employing an integrated approach combining structural biology and biochemistry. Structural analysis reveals that the significant conformational changes in the “lid” region and the peripheral helical domain trigger the switch of the active pocket of PldA to regulate the enzymatic activity. The structure-based mutational experiments identified a series of key residues responsible for substrate hydrolysis activity and the interactions between PldA and PA3488. In summary, this work provides the structural basis for understanding the PldA-mediated invasion of P. aeruginosa and can aid the future drug development targeting PldA.