Molecular mechanism of plant immune receptors discovered

The scientists describe their results in the article 'Direct pathogen-induced assembly of an NLR immune receptor complex to form a holoenzyme' in Science.

Although separated by millions of years of evolution, plants and animals have independently developed similar immune strategies to protect themselves against microbial infections. In both kingdoms of life, immune receptors called nucleotide-binding/leucine-rich repeat proteins (NLR proteins) form an important defence layer within cells against pathogen attack. NLRs are complex devices consisting of several modules. These modules recognize the molecules (effectors) of invading microbes. Effectors trigger the immune response of the plant -- they activate receptors, resistance and cell death pathways to limit infection. Based on different structural and signalling characteristics, plant NLRs are divided into two main classes: those that contain coiled-coiled (CC) modules (CNL proteins) and those that contain toll/interleukin-1 receptor/resistance (TIR) modules (TNL proteins).

The scientists conducted their research on the model organism Arabidopsis thaliana, or thale cress. Jijie Chai, together with the MPIPZ research group leader Jane Parker and MPIPZ dirctor Paul Schulze-Lefert, determined the structural and biochemical features underlying the activation of a specific receptor: the so-called TNL type NLR Receptor of Peronospora parasitica 1 (RPP1). It protects the model plant against infection with the fungus Hyaloperonospora arabidopsidis (Hpa).

To understand how RPP1 protects plants on the molecular level from Hpa infection, the team generated RPP1 protein together with the known Hpa effector ATR1 . The RPP1 receptor activated in this way is an enzyme that breaks down nicotinamide adenine dinucleotide (NAD+), which is important for defence signalling.

By isolating RPP1-ATR1 complexes and subjecting them to cryo electron microscopy, the authors have answered two open questions of NLR biology: first, how direct binding of the effector to the NLR receptor induces the activation of a receptor. Secondly, they determined that the TNL receptor in this case organizes itself as a so-called tetramer, a molecule consisting of four tightly packed receptor molecules. Tetramers belong to the group of oligomeric molecules, which are all structurally made up of similar units. The observed tetramer creates a unique surface within a part of the receptor, which is necessary for the cleavage of NAD+ to trigger defence signals.

The effector ATR1 induces tetramerization at one end of RPP1 and simultaneously forces the above-mentioned four TIR modules at the opposite end of the molecule to form two asymmetric TIR pairs that degrade NAD+.

Strikingly, the results of the groups around Eva Nogales and Brian Staskawicz at the University of California, Berkeley, on another NLR of the TNL type, Roq1 from the tobacco relative Nicotiana benthamiana, also show that TNL activation involves direct effector recognition and 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 discoveries of Jijie Chai, his team and the MPIPZ researchers seem to be of great importance for understanding how these critical plant immune molecules protect their hosts from infections. More generally, the oligomeric configurations adopted by active RPP1 and Roq1 resemble the induced oligomeric scaffolds of other plant and mammalian NLR receptor proteins, including human innate immune receptors. This suggests that these receptors are based on a common structural principle to trigger intracellular immune signals and cell death in different kingdoms of life.