Genome-wide functional analyses of plant coiled–coil NLR-type pathogen receptors reveal essential roles of their N-terminal domain in oligomerization, networking, and immunity

Abstract

The ability to induce a defense response after pathogen attack is a critical feature of the immune system of any organism. Nucleotide-binding leucine-rich repeat receptors (NLRs) are key players in this process and perceive the occurrence of nonself-activities or foreign molecules. In plants, coevolution with a variety of pests and pathogens has resulted in repertoires of several hundred diverse NLRs in single individuals and many more in populations as a whole. However, the mechanism by which defense signaling is triggered by these NLRs in plants is poorly understood. Here, we show that upon pathogen perception, NLRs use their N-terminal domains to transactivate other receptors. Their N-terminal domains homo- and heterodimerize, suggesting that plant NLRs oligomerize upon activation, similar to the vertebrate NLRs; however, consistent with their large number in plants, the complexes are highly heterometric. Also, in contrast to metazoan NLRs, the N-terminus, rather than their centrally located nucleotide-binding (NB) domain, can mediate initial partner selection. The highly redundant network of NLR interactions in plants is proposed to provide resilience to perturbation by pathogens.

An N-terminal motif in NLR immune receptors is functionally conserved across distantly related plant species

“…In plants, NLRs also oligomerize through their N-terminal domains, notably the common and widespread CC domain (Bentham et al, 2018). The CC domain of some, but not all NLRs, triggers cell death when expressed as a truncated domain indicating that it can undertake oligomerization on its own (Maekawa et al, 2011;Casey et al, 2016;Cesari et al, 2016;Wróblewski et al, 2018). However, the molecular mechanisms that underpin CC-NLR activation and subsequent execution of HR cell death have remained largely unknown until very recently.…”

“…The N-terminal CC domain of a subset of CC-NLR proteins can mediate self-association and trigger HR cell death when expressed on its own (Bentham et al, 2018). However, to date truncation experiments have been conducted based on educated guesses of domain boundaries (Maekawa et al, 2011;Casey et al, 2016;Cesari et al, 2016;Wróblewski et al, 2018). Moreover, one amino acid difference in the length of the assayed truncation can affect cell death inducing activity (Casey et al, 2016).…”

Genome-wide functional analysis of hot pepper immune receptors reveals an autonomous NLR cluster in seed plants

“…6). In addition, a recent study reported 346 that 13 of 22 Arabidopsis CNLs in group B that belong to G10 in our classification trigger 347 cell death in Arabidopsis (49). Taken together, these results indicate that many G10-CCs in 348 Solanaceae and Brassicaceae plants have the potential to trigger cell death (SI Appendix, 349 Table S3).…”

“…In addition, a recent study 307 reported that significantly high portion of the predicted CC domain of the CNLs in A. 308 thaliana ecotype Columbia-0 triggered cell death (49). All of the CNLs from group B ).…”

“…One group contains the Toll/interleukin-1 receptor (TIR) domain at 45 the N-terminus, referred as a TIR-type NLR (TNL), whereas the other possesses an NTD 46 with a coiled-coil (CC) structure, referred to as a CNL-type NLR (CNL) (17). One group of 47 CNLs carrying N-terminal CC domains resembling Arabidopsis resistance protein RPW8 was 48 considered to represent a distinct subclass, RPW8-type CNLs (RNL), based on their function 49 in the downstream signaling (19)(20)(21). RNLs are highly conserved in plant species, and they 50 are necessary for the function of other NLRs (21).…”