mTOR complex I (mTORC1) is a central growth regulator that senses amino acids through a pathway that converges on the Rag GTPases, an obligate heterodimer of two related GTPases. Despite their central role in amino acid sensing, it is unknown why the Rag GTPases are heterodimeric and whether their subunits communicate with each other. Here, we find that the binding of guanosine triphosphate (GTP) to one subunit inhibits the binding and induces the hydrolysis of GTP by the other. This intersubunit communication pushes the Rag GTPases into either of two stable configurations, which represent active “on” or “off” states that interconvert via transient intermediates. Subunit coupling confers on the mTORC1 pathway its capacity to respond rapidly to the amino acid level. Thus, the dynamic response of mTORC1 requires intersubunit communication by the Rag GTPases, providing a rationale for why they exist as a dimer and revealing a distinct mode of control for a GTP-binding protein.

mTOR复合物I（mTORC1）是一种中央生长调节剂，可通过会聚在Rag GTPases（两个相关GTPases的专性异二聚体）上的途径来感应氨基酸。尽管它们在氨基酸感测中起着中心作用，但尚不清楚为何Rag GTPases是异二聚体的，以及它们的亚基是否彼此连通。在这里，我们发现鸟苷三磷酸（GTP）与一个亚基的结合抑制了结合，并诱导了另一亚基对GTP的水解。这种亚基间的通讯将Rag GTPases推入两个稳定的配置中的任何一个，它们表示通过瞬态中间体进行相互转换的活动“ on”或“ off”状态。亚基偶联赋予mTORC1途径快速响应氨基酸水平的能力。因此，