The C-terminal tail of Cf resistance proteins determines the intensity of the effector-triggered hypersensitive response-related cell death.

Cf resistance proteins of tomato that provide resistance against the extracellular fungal pathogen Fulvia fulva are receptor-like proteins (RLPs) localized at the cell surface. As they lack a cytoplasmic kinase domain, Cf proteins require 2 co-receptors to activate downstream immune responses. In the resting state, Cf proteins constitutively interact with the receptor-like kinase (RLK) SUPPRESSOR OF BIR1-1 (SOBIR1), whereas upon recognition of the matching avirulence (Avr) effector, the RLK BRI1-ASSOCIATED KINASE 1 (BAK1) is recruited. Cf proteins have a typical leucine-rich repeat (LRR)-RLP structure, consisting of an LRR ectodomain, a transmembrane domain, and an intracellular juxtamembrane domain that is referred to as the C-terminal tail. Cf-4 and Cf-9 have identical C-terminal tails, while the C-terminal tails of Cf-2 and Cf-5 differ by a single amino acid. Interestingly, the Cf-5/Avr5- and Cf-2/Avr2-triggered immune response results in a slower and weaker hypersensitive response (HR)-related cell death than the response triggered by Cf-4/Avr4 and Cf-9/Avr9. Domain swapping between Cf-5 and Cf-9 revealed that the C-terminal tail plays a specific role in determining the intensity of the immune response. Notably, the pool of SOBIR1-associated Cf-4 and Cf-9 proteins is much larger than that of Cf-2 and Cf-5, and a full-length C-terminal tail is required for immune signaling activation. This work provides a basis for further studies on RLP engineering to enhance crop resistance against detrimental pathogens.