Small compounds target environmental stress pathways in plants via the scaffold protein RACK1A
Climate change is predicted to increase water stress on crops and plants in natural communities. RACK1 (Receptor for Activated C Kinase 1) is a highly conserved WD-40 type scaffold protein that regulates diverse signal transduction and stress response pathways in plants. Studies of loss of function mutants in Arabidopsis indicate that RACK1A-the predominant isoform, negatively regulates stress responses that provide drought-resistance and salt tolerance. It is hypothesized that chemical knock-out, as opposed to genetic knockout of RACK1A, will provide a functional advantage in protecting plants from environmental stress. Site-directed mutagenesis studies indicate that key posttranslational modifications, such as tyrosine phosphorylation of Y248 residues, dictate the RACK1A’s function. Using our own published crystal structure of RACK1A protein, dozens of small compounds were identified. These compounds can potentially inhibit the Y248 phosphorylation.
The effectiveness of the compounds in regulating diverse environmental stress responses were evaluated in different crop plants. We found that these compounds protect crops from diverse stresses like drought and salt stresses, by upregulating oxidative stress detoxification pathways. In addition, the developmental pathway associated with the growth hormone auxin appears to be regulated by the compounds as well. Reporter gene assays, tissue cultures, hydroponics and oxidative stress assays were used to establish that the functional inhibitor of RACK1A proteins protects crops from diverse environmental stresses while positively impacting the growth hormone signaling pathway.