@article {67990,
	title = {Cryo-EM structures of the human GATOR1-Rag-Ragulator complex reveal a spatial-constraint regulated GAP mechanism.},
	journal = {Molecular Cell},
	volume = {36},
	year = {2022},
	month = {2022 May 01},
	abstract = {<p>mTORC1 controls cellular metabolic processes in response to nutrient availability. Amino acid signals are transmitted to mTORC1 through the Rag GTPases, which are localized on the lysosomal surface by the Ragulator complex. The Rag GTPases receive amino acid signals from multiple upstream regulators. One negative regulator, GATOR1, is a GTPase activating protein (GAP) for RagA. GATOR1 binds to the Rag GTPases via two modes: an inhibitory mode and a GAP mode. How these two binding interactions coordinate to process amino acid signals is unknown. Here, we resolved three cryo-EM structural models of the GATOR1-Rag-Ragulator complex, with the Rag-Ragulator subcomplex occupying the inhibitory site, the GAP site, and both binding sites simultaneously. When the Rag GTPases bind to GATOR1 at the GAP site, both Rag subunits contact GATOR1 to coordinate their nucleotide loading states. These results reveal a potential GAP mechanism of GATOR1 during the mTORC1 inactivation process.</p>
},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2022.03.002},
	author = {Egri, Shawn B and Ouch, Christna and Chou, Hui-Ting and Yu, Zhiheng and Song, Kangkang and Xu, Chen and Shen, Kuang}
}
@article {65211,
	title = {Cryo-EM structure of the human FLCN-FNIP2-Rag-Ragulator complex.},
	journal = {Cell},
	volume = {179},
	year = {2019},
	month = {2019 Nov 27},
	pages = {1319-29},
	issn = {00928674},
	doi = {10.1016/j.cell.2019.10.036},
	author = {Shen, Kuang and Rogala, Kacper B. and Chou, Hui-Ting and Huang, Rick K. and Yu, Zhiheng and Sabatini, David M.}
}
@article {49123,
	title = {Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes.},
	journal = {Nature},
	volume = {556},
	year = {2018},
	month = {2018 Mar 28},
	pages = {64-9},
	abstract = {<p>Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensitizes mTORC1 signalling to nutrient starvation. GATOR1 components have no sequence homology to other proteins, so the function of GATOR1 at the molecular level is currently unknown. Here we used cryo-electron microscopy to solve structures of GATOR1 and GATOR1-Rag GTPases complexes. GATOR1 adopts an extended architecture with a cavity in the middle; NPRL2 links DEPDC5 and NPRL3, and DEPDC5 contacts the Rag GTPase heterodimer. Biochemical analyses reveal that our GATOR1-Rag GTPases structure is inhibitory, and that at least two binding modes must exist between the Rag GTPases and GATOR1. Direct interaction of DEPDC5 with RAGA inhibits GATOR1-mediated stimulation of GTP hydrolysis by RAGA, whereas weaker interactions between the NPRL2-NPRL3 heterodimer and RAGA execute GAP activity. These data reveal the structure of a component of the nutrient-sensing mTORC1 pathway and a non-canonical interaction between a GAP and its substrate GTPase.</p>
},
	issn = {1476-4687},
	doi = {10.1038/nature26158},
	author = {Shen, Kuang and Huang, Rick K and Brignole, Edward J and Condon, Kendall J and Valenstein, Max L and Chantranupong, Lynne and Bomaliyamu, Aimaiti and Choe, Abigail and Hong, Chuan and Yu, Zhiheng and Sabatini, David M}
}
