Summary
In this paper, Baudin, Schreiber, Martin et al. used structural modelling to identify structural elements required for the self-association of the NLR immune receptor ZAR1, specifically its N-terminal CC-domain ZAR1CC. They used monomeric and dimeric forms of CC domain structure templates available at the time to make ZAR1CC models and tried to map the region involved / responsible for oligomerization. They discovered that the N-terminal α1 helix and EDVID motif in ZAR1CC are important for oligomerization and function of ZAR1. This complements recent findings by Wang et al. (2019) \cite{Wang2019,Wang2019a} based on cryo-EM structures, highlighting the importance of α1 helix for the activity of ZAR1 although some differences were noted that could reflect the different experimental set ups (CC domain vs full-length protein) as discussed in the paper.
They also identified intramolecular interactions between ZAR1 subdomains, notably NB-ARC with CC domain, that keep ZAR1 in an inactive state. They also demonstrated that loss of function mutants in NB-ARC domain do not play a role in interaction with NB-ARC and suppression of ZAR1CC autoactivity.
We believe that this is a nice study that identifies structural elements responsible for CC self-association and is overall consistent with recent structural findings. The set of interaction assays are important to complement the recent findings of ZAR1 cryo-EM structure in inactive and active states. However, in this study, the biological relevance of the NB-ARC/LRR domains in negative regulation of ZAR1 by binding to CC domain is not clear. Detailed comparison between binding affinity of NB-ARC/LRR to CC and the CC-mediated cell death is required for a firm conclusion that intramolecular interactions between ZAR1 subdomains participate in keeping ZAR1 immune complexes inactive.