ArticleNature2018
Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 180 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- GATOR2 regulates the nutrient-dependent recruitment of GATOR1 to lysosomes.bioRxiv : the preprint server for biology · 2026Article
- Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis.Nature cell biology · 2026Article
- Lysosomal phosphoinositide turnover acts upstream of RagGTPase-mTORC1 and controls muscle growth.Nature metabolism · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Architecture of the human KICSTOR and GATOR1-KICSTOR complexes.Nature structural & molecular biology · 2025Article
- Multilayered regulation of TORC1 signaling by Ait1, Gcn2, and SEAC/GATOR during nitrogen limitation and starvation.Nature communications · 2025Article
- The CTLH ubiquitin ligase substrates ZMYND19 and MKLN1 negatively regulate mTORC1 at the lysosomal membrane.Nature communications · 2025Article
- Global conformation of the Rag GTPase heterodimer governs eukaryotic amino acid sensing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural basis for mTORC1 regulation by the CASTOR1-GATOR2 complex.Nature structural & molecular biology · 2025Article
- Article
- Incomplete penetrance and variable phenotypes of a novel NPRL2 frameshift variant: from familial focal epilepsy with variable foci 2 to neurodevelopmental disorders.BMC neurology · 2025Article
- Structural insights into cholesterol sensing by the LYCHOS-mTORC1 pathway.Nature communications · 2025Article
- Review
- Article
- Genotypic and clinical phenotypic analysis of DEPDC5 gene mutations.Neurogenetics · 2025Article
- Uncoupling of Akt and mTOR signaling drives resistance to Akt inhibition in PTEN loss prostate cancers.Science advances · 2025Article
- Neuronal cell type specific roles for Nprl2 in neurodevelopmental disorder-relevant behaviors.Neurobiology of disease · 2025Article
- Heterozygous pathogenic STT3A variation leads to dominant congenital glycosylation disorders and functional validation in zebrafish.Orphanet journal of rare diseases · 2025Article
- Identifying the Pathogenicity of a Novel NPRL3 Missense Mutation Using Personalized Cortical Organoid Model of Focal Cortical Dysplasia.Journal of molecular neuroscience : MN · 2024Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.