Zig, Zag, and ’Zyme: leveraging structural biology to engineer disease resistance

Dynamic host–pathogen interactions determine whether disease will occur. Pathogen effector proteins are central players in such disease development. On one hand, they improve susceptibility by manipulating host targets; on the other hand, they can trigger immunity after recognition by host immune receptors. A major research direction in the study of molecular plant pathology is to understand effector-host interactions, which has informed the development and breeding of crops with enhanced disease resistance. Recent breakthroughs on experiment- and artificial intelligence-based structure analyses significantly accelerate the development of this research area. Importantly, the detailed molecular insight of effector–host interactions enables precise engineering to mitigate disease. Here, we highlight a recent study by Xiao et al., who describe the structure of an effector-receptor complex that consists of a fungal effector, with polygalacturonase (PG) activity, and a plant-derived polygalacturonase-inhibiting protein (PGIP). PGs weaken the plant cell wall and produce immune-suppressive oligogalacturonides (OGs) as a virulence mechanism; however, PGIPs directly bind to PGs and alter their enzymatic activity. When in a complex with PGIPs, PGs produce OG polymers with longer chains that can trigger immunity. Xiao et al. demonstrate that a PGIP creates a new active site tunnel, together with a PG, which favors the production of long-chain OGs. In this way, the PGIP essentially acts as both a PG receptor and enzymatic manipulator, converting virulence to defense activation. Taking a step forward, the authors used the PG-PGIP complex structure as a guide to generate PGIP variants with enhanced long-chain OG production, likely enabling further improved disease resistance. This study discovered a novel mechanism by which a plant receptor plays a dual role to activate immunity. It also demonstrates how fundamental knowledge, obtained through structural analyses, can be employed to guide the design of proteins with desired functions in agriculture.