Tandem kinase proteins and kinase-fusion architectures in plant immune system.

Tandem kinase proteins (TKPs) and kinase fusion proteins (KFPs) have emerged as a major class of intracellular immune receptors that complement classical pattern-recognition receptors (PRRs) and nucleotide-binding leucine-rich repeat (NLR) sensors in plants. These receptors integrate active kinases, pseudokinases, and diverse integrated domains to create versatile effector-recognition platforms capable of detecting rapidly evolving pathogen effectors. Recent work across wheat, barley, and their wild relatives has revealed that TKPs operate through a conserved sensor-switch-executor logic in which effector binding to a regulatory kinase domain alleviates autoinhibition, enabling activation of paired NLRs that assemble resistosomes and initiate defense. Systems such as Sr62TK-Sr62NLR, WTK3/Pm24-WTN1, Rwt4, WTK1/Yr15, WTK7-TM/Pm36, Pm13 (MLKL-K), Pm4, Pm57, and Lr9/WTK6-vWA illustrate the diverse mechanisms and evolutionary patterns of TKP- and KFP-mediated immunity. Genome-wide surveys identify hundreds of TKPs across land plants, with extensive domain innovation and strong signatures of positive selection in the Triticeae. Recent high-quality pangenomes, as well as effector library screening, phosphoproteomics, and live-cell imaging now enable systemic discovery and functional validation of TKPs. Machine learning further accelerates this process by predicting effector-binding surfaces, mapping kinase-pseudokinase allostery, and guiding rational engineering of chimeric or gain-of-function variants. These insights open new translational avenues including deploying wild-relative TKPs into elite cultivars, tuning activation thresholds through precise gene editing, and designing synthetic immune circuits for multi-effector recognition. As global agriculture faces intensifying pathogen pressures, TKP- and KFP-based immunity offers a powerful and sustainable strategy for developing resilient crops and strengthening long-term food security.