A novel conserved mechanism for plant NLR protein pairs: the "integrated decoy" hypothesis

Abstract

Plant immunity is often triggered by the specific recognition of pathogen effectors by intracellular nucleotide-binding, leucine-rich repeat receptors (NLR). Plant NLRs contain an N-terminal signaling domain that is mostly represented by either a Toll-interleukin1 receptor (TIR) domain or a coiled coil (CC) domain. In many cases, single NLR proteins are sufficient for both effector recognition and signaling activation. However, many paired NLRs have now been identified where both proteins are required to confer resistance to pathogens. Recent detailed studies on the Arabidopsis thaliana TIR-NLR pair RRS1 and RPS4 and on the rice CC-NLR pair RGA4 and RGA5 have revealed for the first time how such protein pairs function together. In both cases, the paired partners interact physically to form a hetero-complex receptor in which each partner plays distinct roles in effector recognition or signaling activation, highlighting a conserved mode of action of NLR pairs across both monocotyledonous and dicotyledonous plants. We also describe an "integrated decoy" model for the function of these receptor complexes. In this model, a plant protein targeted by an effector has been duplicated and fused to one member of the NLR pair, where it acts as a bait to trigger defense signaling by the second NLR upon effector binding. This mechanism may be common to many other plant NLR pairs.

Keywords: Arabidopsis thaliana; NLR protein pairs; integrated decoy; pathogen recognition; plant immunity; rice.

Figure 1

Functional models of RPS4/RRS1 and RGA4/RGA5 NLR pairs. In the inactive state, co-acting NLRs form a hetero-complex in which the signaling NLR (RPS4 or RGA4) is repressed by the AVR-receptor NLR (RRS1 or RGA5). After pathogen challenge, direct recognition of AVR proteins by the receptor NLR partner (RRS1 or RGA5) occurs. In the case of RGA5, AVR-binding involves the C-terminus containing the RATX1 domain while RRS1 interacts with PopP2 and AvrRps4 through its WRKY domain (Jones and Deslandes, personal communication). After AVR-recognition, NLR hetero-complexes are still present in both cases. Induction of HR by RPS4/RRS1 involves disruption of TIR domains hetero-interaction and subsequent homo-dimerization of RPS4 TIR domain. In the case of RGA4 and RGA5, we cannot rule out that induction of HR requires disruption of RGA4 and RGA5 hetero-complexes. Hence, two hypothetical models are proposed. According to the first model, HR is induced by RGA4 homo-complex freed from the RGA5/AVRs complex, whereas, in the second model, conformational changes within the RGA4/RGA5 hetero-complex would allow RGA4 to signal. N, N-terminal; C, C-terminal; TIR, Toll/interleukin1 receptor; CC, coiled coil; NBS, nucleotide binding site; NB, nucleotide binding; ARC, Apaf-1, R-protein and CED-4; LRR, leucine-rich repeats; HR, hypersensitive response.

Figure 2

Model of integrated decoys in NLR protein pairs. Pathogen effectors target host proteins for manipulation in order to promote infection. Indirect recognition of these effectors occurs when these target proteins are guarded by host NLR proteins (1), or if duplicated target genes evolve into decoy proteins monitored by host NLRs (2). Alternatively the decoy may be integrated into the structure of the receptor component of an NLR pair (3), allowing AVR recognition by direct binding.