Structural basis of NLR activation and innate immune signalling in plants

Abstract

Animals and plants have NLRs (nucleotide-binding leucine-rich repeat receptors) that recognize the presence of pathogens and initiate innate immune responses. In plants, there are three types of NLRs distinguished by their N-terminal domain: the CC (coiled-coil) domain NLRs, the TIR (Toll/interleukin-1 receptor) domain NLRs and the RPW8 (resistance to powdery mildew 8)-like coiled-coil domain NLRs. CC-NLRs (CNLs) and TIR-NLRs (TNLs) generally act as sensors of effectors secreted by pathogens, while RPW8-NLRs (RNLs) signal downstream of many sensor NLRs and are called helper NLRs. Recent studies have revealed three dimensional structures of a CNL (ZAR1) including its inactive, intermediate and active oligomeric state, as well as TNLs (RPP1 and ROQ1) in their active oligomeric states. Furthermore, accumulating evidence suggests that members of the family of lipase-like EDS1 (enhanced disease susceptibility 1) proteins, which are uniquely found in seed plants, play a key role in providing a link between sensor NLRs and helper NLRs during innate immune responses. Here, we summarize the implications of the plant NLR structures that provide insights into distinct mechanisms of action by the different sensor NLRs and discuss plant NLR-mediated innate immune signalling pathways involving the EDS1 family proteins and RNLs.

Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity

“…Activated ETI signaling results in pathogen restriction and often a host hypersensitive cell death response (HR) at infection sites ( 4 ). Direct or indirect recognition of effectors induces NLR oligomerization ( 5 ), resulting in formation of large protein complexes termed resistosomes ( 1, 6, 7 ). The Arabidopsis CNL ZAR1 resistosome functions as a calcium-permeable channel for ETI signaling ( 8 ).…”

“…Nucleotide-binding leucine-rich repeat (NLR) proteins are intracellular immune receptors with crucial roles in innate immunity of plants and animals ( 1 ). Plant NLRs have a conserved organization with a central nucleotide-binding domain (NBD), a C-terminal leucine-rich repeat (LRR) domain and an N-terminal coiled-coil (CC) or Toll/interleukin-1 receptor domain, referred to as CNL or TNL receptors, respectively.…”

Chemical structures of cyclic ADP ribose (cADPR) isomers and the molecular basis of their production and signaling

“…The ~150-residue TIR (Toll/interleukin-1 receptor) domains are widely distributed in animals, plants and bacteria, and function through self-association and homotypic interactions with other TIR domains (1). In plants and animals, these domains are predominantly found in proteins with immune functions such as TLRs (Toll-like receptors), IL-1Rs (interleukin-1 receptors) and their adaptor proteins (2)(3)(4)(5), and plant NLRs (nucleotide-binding, leucine-rich repeat receptors) (6,7). TIR domains form higher-order oligomers and orchestrate signal amplification by a mechanism referred to as signaling by cooperative assembly formation (SCAF) (6,(8)(9)(10).…”

The Roles of NOD-like Receptors in Innate Immunity in Otitis Media

“…NLRs have been classified into several subclasses, NLRA, NLRB, NLRC and NLRP, based on the combination of N-terminal effector domains, including the transactivator domain (AD), baculovirus inhibitor repeats (BIRs), caspase recruitment domain (CARD), and pyrin domain (PYD). The central NOD domain possesses ATPase activity and is involved in NLR oligomerization [35,36]. NLRs are PRRs expressed in the cytosol and are composed of an LRR domain that recognizes a ligand, a NACHT domain for oligomerization of LRR, and a CARD or pyrin domain that directly binds to signaling molecules and transmits a signal.…”