Pratheek Pandesha (@hadse.bsky.social)

An effector from the potato late blight pathogen bridges ENTH-domain protein TOL9a to an activated helper NLR to suppress immunity Pathogens counteract central nodes of NLR immune receptor networks to suppress immunity. However, the mechanisms by which pathogens hijack helper NLR pathways are poorly understood. Here, we show that an effector from the potato late blight pathogen Phytophthora infestans bridges the host protein NbTOL9a, a putative member of the host ESCRT pathway, to a helper NLR to suppress immunity. In this work, we solved the crystal structure of the RXLR-LWY effector AVRcap1b in complex with the ENTH domain of NbTOL9a. The structure revealed that unlike other RXLR-LWY effectors, AVRcap1b has a novel L-shaped fold and defines a new structural family of effectors in the Phytophthora genus. Moreover, we defined the AVRcap1b/NbTOL9a binding interface and designed effector mutants that don't bind NbTOL9a, impairing immune suppression. This indicates that ENTH binding is required for full virulence activity of this effector. Lastly, we show that AVRcap1b associates specifically with activated NbNRC2 independently of NbTOL9a binding. This suggests that the effector functions as a bridge that interconnects NbNRC2 with the NbTOL9a pathway. These results illustrate an unprecedented pathogen mechanism to hijack helper NLR pathways and suppress immunity. ### Competing Interest Statement T.O.B. and S.K. receive funding from industry on NLR biology and cofounded a start-up company (Resurrect Bio Ltd.) on resurrecting disease resistance. M.P.C., L.D., and S.K. have filed patents on NLR biology. M.P.C. and L.D. have received fees from Resurrect Bio Ltd. The other authors declare that they have no competing interests. European Research Council, https://ror.org/0472cxd90, 743165 British Society for Plant Pathology, https://ror.org/04zj17j36 Biotechnology and Biological Sciences Research Council, BB/P012574, BBS/E/J/000PR9795, BBS/E/J/000PR9796, BBS/E/J/000PR9797, BBS/E/J/000PR9798, BB/V002937/1 https://www.biorxiv.org/content/10.1101/2025.07.06.663370v1