Detalle de: Structural basis for the recruitment and activation of the Legionella phospholipase VipD by the host GTPase Rab5

Significance A long-standing question in the field of microbial pathogenesis is how virulence factors are regulated within host cells and how their activity is specifically directed toward a particular host cell compartment. Legionella pneumophila resolves this dilemma by tightly coupling the phospholipase A1 activity of one of its effectors, vacuolar protein sorting inhibitor protein D (VipD), to this protein’s interaction with endosomal host GTPases. We now present the crystal structure of VipD in complex with host cell Rab5c, providing a detailed look into the ingenious molecular mechanisms underlying the allosteric activation of a virulence factor by a host protein and its spatiotemporal regulation. These results open the path for the development of novel therapeutics aimed at blocking the VipD activation process rather than the enzyme’s active site.