Pathogen protein modularity enables mimicry of a host phosphatase

Pathogens rely on a diverse complement of effector proteins to manipulate host cellular processes. The devastating plant pathogen Phytophthora produces numerous effectors that consist of tandem repeats of the “(L)WY” motif. Here, we discovered a specific (L)WY-LWY combination that enables efficient recruitment of the Serine/Threonine protein phosphatase 2A (PP2A) core enzyme in plant hosts. Structural characterization of an effector-PP2A complex and biochemical analyses demonstrate multiple effectors adopt this module at the amino terminus to form functional PP2A holoenzymes but have divergent C-terminal LWY units. Our results discovered a virulence strategy widely employed by Phytophthora in which an essential phosphatase complex of the host is appropriated to promote disease and highlight how diversification in an effector repertoire is promoted by protein modularity.