Zheng, NingGish, Madeline2025-08-012025-08-012025-08-012025Gish_washington_0250E_28608.pdfhttps://hdl.handle.net/1773/53734Thesis (Ph.D.)--University of Washington, 2025Humans are dependent on plants for food, energy and materials, yet plants are constantly under threat from bacteria, viruses and insects. Plants defend themselves from pathogens primarily through the expression of specialized defense genes, initiated by the key defense hormone salicylic acid, which is structurally related to the drug aspirin. Defense gene transcription and translation is a massive metabolic commitment by the plant, requiring tight negative control for long-term plant health. The salicylic acid receptor, NPR1, interacts with transcription factors to initiate defense gene transcription through an unknown mechanism. The Nimin family of proteins, under the control of an SA responsive promoter, form a negative feedback loop by directly interacting with NPR1 to stop defense gene transcription. The mechanism of this interaction, although necessary for control of the plant immune response, is poorly defined. In this work, I present the first biophysical characterization of NPR1’s interaction with the Nimin family of proteins and report the x-ray crystal structure of NPR1 salicylic acid binding domain in complex with Nimin-1, showing separate Nimin and SA binding pockets. I then demonstrate that Nimin-1 proteins regulate NPR1 signaling by allosterically competing with salicylic acid to bind to NPR1’s C-terminal domain, and further identify key residues in the allosteric pathway between the two pockets.application/pdfen-USCC BY-NC-SANimin-1NPR1plant immunitySalicylic AcidPharmacologyBiologyBotanyPharmacologyThesis