Interaction between Rheb and NR1 (6BT0)

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Rheb is a protein that exists independently, with a molecular weight of approximately 21 kilodaltons and plays a pivotal role in activating the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 is a master regulator of cellular growth and metabolism, also influencing protein synthesis significantly. Several chronic diseases have been linked to aberrant mTORC1 activity, making this area an essential focus for ongoing research. NR1 acts as an inhibitor of Rheb by selectively blocking mTORC1 signaling pathways through occupation of the hydrophobic pocket within the switch II domain of Rheb. By inhibiting Rheb, NR1 functions as a potential therapeutic target in mTORC1 signaling. Nat Commun 2018;9(1):548 reports on a small molecule inhibitor of Rheb that targets mTORC1 signaling specifically.