NR1 binding to Rheb blocks mTORC1 signalling
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Rheb is a small GTPase that activates the kinase activity of mammalian target of rapamycin complex 1(mTORC1) in response to growth factor signals. mTORC1 is a key regulator of cellular growth and proliferation by driving the phosphorylation of S6K1 that acts downstream of the PI3 kinase pathway. When NR1, a selective inhibitor, binds to the switch II domain of Rheb, the activation of mTORC1 is inhibited. This model shows the interactions between NR1 and Rheb switch II domain, along with the conformational changes that lead to unfavourable mTORC1-Rheb binding. Inhibition of Rheb by NR1 can serve as a pharmacological model for potential therapeutic drugs that aim to selectively inhibit mTORC1. References: 10.1038/s41467-018-03035-z 10.1074/jbc.M610736200
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