Structural and functional study of the Legionella pneumophila effector protein Lpg0393

Abstract

Legionella pneumophila is a human intracellular pathogen which encodes about 290 effector proteins, which are translocated into host cells through a secretion system. Only a few effector proteins have been shown to manipulate cellular processes during infection while the functional roles of the remaining majority are still unknown. Lpg0393 is an experimentally identified effector protein classified as a hypothetical protein. Through structural analysis using X-ray crystallography, I showed that Lpg0393 contains a Vps9-like domain which activates endosomal Rab proteins Rab5, Rab21 and Rab22. Consistently, Lpg0393 had a guanine-nucleotide exchange factor activity toward the Rab5 sub-cluster members. This study identifies the first case of a bacterial guanine-nucleotide exchange factor activating the endosomal Rab proteins, implying that the activation of these Rab proteins might be beneficial for the intracellular survival of Legionella pneumophila.