A plant immune receptor: four are enough to tango

Although separated by millions of years of evolution, plants and animals have self-interested in similar innate immune strategies to protect themselves from microbial infections. In both realms of life, immune receptors called nucleotide binding proteins / leucine-rich proteins (NLRs) form an important defense layer within cells against pathogen attack. NLRs are complex devices made up of several modules that recognize molecules from invading microbes called effectors and then locally activate resistance and cell death pathways to limit infection. Based on distinct structural and signaling characteristics, plant NLRs are divided into two main classes: those that contain Coiled-Coiled (CC) modules (CNL proteins) and those that host Toll / receptor / resistance modules of interleukin- 1 (TIR) ​​(TNL proteins). In a recent study, MPIPZ researchers and Humboldt’s Professor Jijie Chai and his team were able for the first time to piece together the sequence of molecular events that convert an inactive TNL-type plant immune receptor into an active resistosome complex. which mediates the death of host cells.

Chai, who is also affiliated with the University of Cologne, joined forces with research group leader Jane Parker and MPIPZ director Paul Schulze-Lefert to determine the structural and biochemical characteristics underlying the activation of recognition of the Peronospora parasitica 1 (RPP1) TNL-type NLR receptor, which protects the model plant Arabidopsis thaliana from infection with the oomycete pathogen Hyaloperonospora arabidopsidis (Hpa). To understand at the molecular level how RPP1 protects plants from Hpa infection, Chai, Schulze-Lefert, Parker and colleagues expressed RPP1 along with a recognized Hpa effector ATR1 protein in insect cells, a system that allows for high levels of protein expression. . The RPP1 receptor activated by ATR1 is an enzyme that breaks down nicotinamide adenine dinucleotide (NAD +), which is important for defense signaling.

By isolating RPP1-ATR1 oligomeric complexes and subjecting them to cryo-electron microscopy, the authors answered two outstanding questions in NLR biology: how direct effector binding induces conformational activation of an NLR receptor and how the oligomer organization of the TNL receptor (in this case a tetramer composed of four tightly packed receptor molecules) creates a unique surface within a portion of the receptor, which is required to cleave NAD + to initiate defense signaling. In particular, the tetramerization of RPP1 induced by ATR1 at one end of the receptor complex forces – at the opposite end – the four TIR modules to form two pairs of asymmetric TIRs, which are the NAD + rupture sites (Figure 1). Thus, the RPP1 resistosome functions as a “holoenzyme”, the active form of an enzyme for cleaving NAD.

Surprisingly, the results from the groups of Eva Nogales and Brian Staskawicz at the University of California, Berkeley, on another TNL-type NLR, Roq1 of the tobacco relative Nicotiana benthamiana, also show that TNL activation involves direct recognition of the effector and the adoption of a similar tetrameric structure. The effector recognized by Roq1 is produced by a bacterial pathogen and the activated Roq1 receptor complex provides resistance to bacterial infections. Therefore, the findings of the MPIPZ researchers appear to have broad relevance for understanding how these critical plant immune molecules protect their hosts from infection. More generally, the oligomeric configurations adopted by active RPP1 and Roq1 resemble induced oligomeric scaffolds of other plant and mammalian NLR receptor proteins, including human innate immune system receptors. This suggests that these receptors rely on a common structural principle to initiate intracellular immune signaling and cell death in different realms of life.

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Additional multimedia contacts

Paul Schulze-Lefert,
email: [email protected]

Jane Parker,
email: [email protected]