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Rag–Ragulator is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway
Proceedings of the National Academy of Sciences of the United States of America 121 (35): e2322755121 (2024)
The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth and metabolism in response to many environmental cues, including nutrients. Amino acids signal to mTORC1 by modulating the guanine nucleotide loading states of the heterodimeric Rag GTPases, which bind and recruit mTORC1 to the lysosomal surface, its site of activation. The Rag GTPases are tethered to the lysosome by the Ragulator complex and regulated by the GATOR1, GATOR2, and KICSTOR multiprotein complexes that localize to the lysosomal surface through an unknown mechanism(s). Here, we show that mTORC1 is completely insensitive to amino acids in cells lacking the Rag GTPases or the Ragulator component p18. Moreover, not only are the Rag GTPases and Ragulator required for amino acids to regulate mTORC1, they are also essential for the lysosomal recruitment of the GATOR1, GATOR2, and KICSTOR complexes, which stably associate and traffic to the lysosome as the “GATOR” supercomplex. The nucleotide…
Discovery of highly potent SARS-CoV-2 nsp14 methyltransferase inhibitors based on adenosine 5′-carboxamides
RSC Medicinal Chemistry 2024: Early View
Developing and Benchmarking Sulfate and Sulfamate Force Field Parameters via Ab Initio Molecular Dynamics Simulations To Accurately Model Glycosaminoglycan Electrostatic Interactions
Journal of Chemical Information and Modeling 2024: Early View
NMR screen reveals the diverse structural landscape of a G-quadruplex library
Chemistry - A European Journal 2024: Early View