Structure and mechanism of bacterial effectors that hijack trafficking small GTPases (LB278)

Abstract

Membrane traffic, which is the “cellular postal service” that shuttles biomolecules around the cell and organizes the structure of organelles, is among the primary targets of effectors injected by intracellular pathogenic bacteria to invade their host and avoid from being destroyed. We will present our recent structural and biochemical studies of effectors from Legionella pneumophila (the bacteria that causes the legionnaire’s disease, a severe pneumonia) which divert membrane traffic to generate a membrane‐bound vacuole where the pathogen hides and replicates. One of these effectors, AnkX, is a FIC domain‐containing toxin that alters the functions of a Rab GTPase involved in vesicular traffic at the endoplasmic reticulum, by covalent attachment of a phosphocholine molecule. The other one, RalF, functions as an illegitimate guanine nucleotide exchange factor to illegitimately activate an Arf GTPase on the vacuole. Our studies showed how AnkX binds and process CDP‐choline to transfer phosphocholine to Rab1 [1], and uncover a novel membrane sensor in RalF that controls its localization and activity [2] [1] Campanacci V, Mukherjee S, Roy CR, Cherfils J. The mechanism of phosphocholine transfer by AnkX, an ankyrin repeats and FIC domain‐containing Legionella effector. EMBO J. (2013) 32:1469‐77.[2] A Novel Membrane Sensor Controls the Localization and ArfGEF Activity of Bacterial RalF. Folly‐Klan M, Alix E, Stalder D, Ray P, Duarte LV, Delprato A, Zeghouf M, Antonny B, Campanacci V, Roy CR, Cherfils J. PLoS Pathog. (2013) 9(11):e1003747.Grant Funding Source: Supported by CNRS and ANR