NR1 inhibits the Rheb-mTORC1 interaction

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mTORC1 is part of the Ser/Thr kinase family and is a master regulator of cellular growth and metabolism. It interacts with a GTP-binding protein, Rheb, which contains a Switch 2 region. This region binds to the mTOR catalytic domain and activates it. The mTORC1 signaling pathway modulates protein synthesis by phosphorylating translational regulators, so its activation must be regulated. Aberrant mTORC1 signaling is associated with cancer, where cells drive neoplastic growth by activating proteins that perform neovascularisation and proliferation. Thus inhibitors are needed to bring the signaling under control. While previous inhibitors have caused side effects (hyperglycaemia and adverse renal function) due to issues with specificity, NR1 is a more potent inhibitor of mTORC1 by binding to the Rheb Switch 2 domain. This tour (PDB: 6BT0) initially focuses on how NR1 inhibits the Rheb-mTORC1 interaction, followed by how NR1 is stabilized in the Switch 2 domain. https://www.nature.com/articles/s41467-018-03035-z