Abstract 2086 Local Changes, Global Impacts: Investigating How Local Manipulations Alter Global Conformations in the Rag GTPase Heterodimer Using smFRET

Balancing anabolic and catabolic processes is crucial for eukaryotic cells to coordinate nutrient and metabolite levels across organelles. Central to this regulation is the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which integrates nutrient signals from recycled organelles, lysosomes, and late endosomes. Activation of mTORC1 in nutrient-rich conditions requires its anchoring to lysosomes by the Rag GTPases. Here, I investigate how local manipulations, such as small-molecule binding and mutations, regulate the global conformation of the Rag GTPase heterodimer, and thus how amino acid signals are transmitted to mTORC1.