Balanced plant helper NLR activation by a modified host protein complex

Abstract

Nucleotide-binding leucine-rich repeat (NLR) receptors play crucial roles in plant immunity by sensing pathogen effectors¹. In Arabidopsis, certain sensor NLRs function as NADases to catalyse the production of second messengers^2,3, which can be recognized by enhanced disease susceptibility 1 (EDS1) with its partner senescence-associated gene 101 (SAG101), to activate helper NLR N requirement gene 1 (NRG1)⁴. A cryoelectron microscopy structure shows that second-messenger-activated EDS1-SAG101 mainly contacts the leucine-rich repeat domain of NRG1A to mediate the formation of an induced EDS1-SAG101-NRG1A complex. Structural comparisons show that binding of a second messenger induces conformational changes in EDS1-SAG101, which are recognized by NRG1A, leading to its allosteric activation. We further show that an inhibitory NRG1 family member, NRG1C, efficiently outcompetes NRG1A for binding to second-messenger-activated EDS1-SAG101. These findings uncover mechanisms for NRG1A activation through its recognition of a modified host EDS1-SAG101 complex, and NRG1A inhibition by NRG1C through sequestration of the activated EDS1-SAG101, thus shedding light on the activation and constraint of a central plant immune response system.