ArticleNature communications2021
Structural insights into TSC complex assembly and GAP activity on Rheb.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 102 citations in OpenAlex.
- Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.Nature communications · 2026Article
- Correlations between TSC Expression and Menorrhagia in Adenomyosis Patients.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- An integrated, scaled approach to resolve TSC2 variants of uncertain significance.Nature communications · 2026Article
- Insights into the function and structure of the R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) chaperone complex.Cell stress & chaperones · 2026Review
- AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.Molecular cancer · 2026Article
- AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.Research square · 2026Article
- Molecular Characterization ofHuman mutation · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
- HCMV immediate-early protein IE2 induces neurotoxicity and hearing loss by disrupting TSC2-mTOR signaling and metabolic homeostasis.Journal of neuroinflammation · 2025Article
- HSV-1 US3: A Master Mimic Hijacking Host Kinase Networks for Viral Dominance.Journal of medical virology · 2025Review
- Mitochondrial metabolic rewiring sensitizes mTORC1 inhibitor persister cells to cuproptosis.JCI insight · 2025Article
- Uncomplexed-TSC1 deploys novel mTORC1-independent pathway to exacerbate the liver glycogen storage in TSC.Cell death & disease · 2025Article
- Amino acid-dependent TSC2 dephosphorylation by lysosome-PP2A regulates mTORC1 signaling transduction.Life science alliance · 2025Article
- Structure and mechanism of the RalGAP tumor suppressor complex.Nature communications · 2025Article
- V-ATPase and Lysosomal Energy Sensing in Periodontitis and Medicine-Related Osteonecrosis of the Jaw.Biomolecules · 2025Review
- Evolution of growth factor signaling to the TSC complex to regulate mTORC1.Science signaling · 2025Review
- The role of autophagy in fibrosis: Mechanisms, progression and therapeutic potential (Review).International journal of molecular medicine · 2025Review
- Unraveling the Binding Mode of TSC2-Rheb through Protein Docking and Simulations.Biochemistry · 2025Article
- Nutritional Interventions to Attenuate Quadriceps Muscle Deficits following Anterior Cruciate Ligament Injury and Reconstruction.Sports medicine (Auckland, N.Z.) · 2025Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small GTPase Rheb and inhibits Rheb-mediated activation of mTORC1. Mutations in TSC genes cause tuberous sclerosis. In this study, the near-atomic resolution structure of human TSC complex reveals an arch-shaped architecture, with a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7. This asymmetric complex consists of two interweaved TSC1 coiled-coil and one TBC1D7 that spans over the tail-to-tail TSC2 dimer. The two TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1. Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb. Our study reveals mechanisms of TSC complex assembly and GAP activity.
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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.