DSSS - Modularity-driven diversification of pathogen effectors

The dynamic interplay between virulence factors of a pathogen and the immune system of a host determines whether disease will occur. A deep understanding of the molecular mechanisms that underlie host-pathogen arms race is essential for developing durable disease resistance. Plant pathogens have evolved a large and diverse complement of virulence proteins, called effectors, which, collectively, are indispensable for disease development. However, how functional diversity is generated in an effector repertoire is poorly understood. We are interested in understanding the molecular mechanisms that promote effector evolution using the devastating Phytophthora pathogens as a model. We found that many Phytophthora effectors contain the “(L)WY” motifs, which are structurally conserved but variable in sequences. Moreover, individual (L)WY units often form tandem repeats in effectors through a conserved concatenation mechanism. We now have evidence that (L)WY motifs are functional modules with specific unit or unit combination mediating interactions with specific host target(s). In particular, we discovered a (L)WY-LWY module that can efficiently recruit the Ser/Thr protein phosphatase 2A core enzyme in plant hosts, allowing the formation of functional effector-PP2A holoenzymes. Importantly, effectors sharing the PP2A-interacting module at the Amino terminus possess divergent C-terminal LWY units, thereby regulating distinct sets of phosphoproteins in the host. This work highlights the appropriation of an essential host phosphatase through a molecular mimicry as a pathogen innovation. I will discuss how functional diversification can be promoted by the modular architecture of effector proteins, through which novel virulence activities may be created.