Subversive bacteria reveal new tricks in their cytoskeleton-hijacking arsenal

Abstract

During infection, pathogenic Yersinia species secrete the antiphagocytic factor YopO (or YpkA), which contains a kinase domain and a Rho GTPase guanine nucleotide dissociation inhibitor (GDI) domain. The structure of YopO in complex with actin and biochemical analyses reveal the mechanism by which YopO uses actin to activate its kinase domain and recruit, phosphorylate and deactivate actin-assembly factors implicated in phagocytic clearance of the bacterium.

Figure 1. Mechanism of YopO-mediated cytoskeleton disassembly

A Yersinia cell establishes a first contact with a phagocyte through adhesin-receptor interactions. The bacterium deploys a syringe-like T3SS and injects several effector proteins into the eukaryotic host, including six Yops. YopO is targeted to the plasma membrane via its N-terminal domain, where it interacts with Rho-family GTPases through its GDI domain and recruits an actin monomer through interactions with both the GDI and kinase domains. Since Yersinia spp. inject only minute amounts of Yops into target cells where actin is the most abundant protein, actin monomer sequestration by YopO is unlikely to have a substantial effect on the eukaryotic cytoskeleton. Instead, YopO disposes of two more efficient strategies to impair the cytoskeleton: downregulation, via its GDI domain, of Rho-family GTPases that control cytoskeleton assembly, and sequestration and/or phosphorylation-dependent inactivation of cytoskeleton assembly factors. These factors include WASP-family proteins that act as Nucleation Promoting Factors (NPFs) for the Arp2/3 complex, VASP-family proteins that control filament elongation, formins that control the nucleation and elongation of non-branched actin networks, and gelsolin, a filament severing protein.