Research Article

Architecture of human Rag GTPase heterodimers and their complex with mTORC1

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Science  11 Oct 2019:
Vol. 366, Issue 6462, pp. 203-210
DOI: 10.1126/science.aax3939

Mastering regulation

The mechanistic target of rapamycin complex 1 (mTORC1) is known as the master kinase, acknowledging its key role in integrating multiple signals to regulate cell growth. When nutrients are abundant, heterodimers of Rag, a class of small guanosine triphosphatase, bind to mTORC1 and recruit it to the lysosome. Here, other signaling pathways converge on the mTORC1 complex. Anandapadamanaban et al. determined cryo–electron microscopy and crystal structures of a RagA/RagC heterodimer. The structures, together with dynamic studies, explain the nucleotide states required for binding to mTORC1 and support a mechanism for conformational communication between the RagA and RagC subunits in the heterodimer. RagA/RagC binding causes no conformational change in mTORC1, which is consistent with the idea that mTORC1 must sense additional growth regulators before it is activated.

Science, this issue p. 203

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