Seeing is believing: Understanding functions of NPR1 and its paralogs in plant immunity through cellular and structural analyses

In the past 30 years, our knowledge of how nonexpressor of pathogenesis-related genes 1 (NPR1) serves as a master regulator of salicylic acid (SA)-mediated immune responses in plants has been informed largely by molecular genetic studies. Despite extensive efforts, the biochemical functions of this protein in promoting plant survival against a wide range of pathogens and abiotic stresses are not completely understood. Recent breakthroughs in cellular and structural analyses of NPR1 and its paralogs have provided a molecular framework for reinterpreting decades of genetic observations and have revealed new functions of these proteins. Besides NPR1's well-known nuclear activity in inducing stress-responsive genes, it has also been shown to control stress protein homeostasis in the cytoplasm. Structurally, NPR4's direct binding to SA has been visualized at the molecular level. Analysis of the cryo-EM and crystal structures of NPR1 reveals a bird-shaped homodimer containing a unique zinc finger. Furthermore, the TGA32-NPR12-TGA32 complex has been imaged, uncovering a dimeric NPR1 bridging two TGA3 transcription factor dimers as part of an enhanceosome complex to induce defense gene expression. These new findings will shape future research directions for deciphering NPR functions in plant immunity.