Cladosporium fulvum effector Ecp6 outcompetes host immune receptor for chitin binding through intrachain LysM dimerization

Successful pathogens secrete effector proteins to deregulate host immunity which is triggered upon detection of pathogen-associated molecular patterns (PAMPs). Several fungal pathogens employ LysM effectors, such as Ecp6 from Cladosporium fulvum, to sequester fungal cell wall-derived chitin oligomers which act as PAMP and would otherwise be recognized by host immune receptors and trigger defense responses. The mechanism by which LysM effectors scavenge chitin molecules remained unknown thus far. Based on crystal structure analysis of Ecp6, we reveal a novel mechanism for chitin binding by intrachain LysM dimerization, leading to a binding groove in which chitin is deeply buried in the effector protein. Isothermal titration calorimetry experiments show that the concerted action of two LysM domains mediates a single chitin binding event with ultra-high (pM) affinity.