Structural bases of the regulation of the pathways leading to salt tolerance in plants

One significant abiotic stressor that reduces crop productivity globally is soil salt. Calcium-mediated reactions that preserve ionic homeostasis in saline environments depend on the Salt Overly Sensitive (SOS) signalling pathway, namely the SOS3 (CBL4)–SOS2 (CIPK24) complex. This work explains how to modulate the formation of this complex using a biochemical method to find compounds of small molecular weight that can interact with SOS3. Using high-resolution structural data and fragment-based pocket analysis, a virtual screening campaign and molecular docking to identify candidate compounds were performed. Two molecules, PC267 and PC341, were selected based on their docking scores and pharmacophoric compatibility. Using Microscale Thermophoresis, their binding to SOS3 was verified, and dissociation values in the micromolar range were obtained. In agreement with previous in vivo analysis using a reconstituted yeast SOS system, functional tests showed that PC267 improves tolerance to salt stress, but PC341 inhibits it. According to structural investigations, the chemicals modify conformational loops essential for SOS2 activation by interacting with different areas of the SOS3 binding pocket. These results establish SOS3 as a target that may be chemically targeted and provide a foundation for the creation of nongenetic methods to increase crop resistance to salinity.