NR1 binding to Rheb blocks mTORC1 signalling
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Rheb is a small GTPase that unleashes the kinase activity of mammalian target of rapamycin complex 1 (mTORC1) in response to growth factor signals. mTORC1 plays a pivotal role in regulating cellular growth and proliferation by driving the phosphorylation of S6K1, which 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 blocked. This model depicts the interactions between NR1 and Rheb's switch II domain, as well as the conformational changes that lead to unfavorable mTORC1-Rheb binding. Inhibition of Rheb by NR1 can serve as a pharmacological model for potential therapeutic drugs designed to selectively inhibit mTORC1.
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