ArticleJournal of molecular biology2021
Architecture of the Tuberous Sclerosis Protein Complex.
Article in Journal of molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- An integrated, scaled approach to resolve TSC2 variants of uncertain significance.Nature communications · 2026Article
- Genotype and Cardiac Rhabdomyoma Phenotype Analyses in Tuberous Sclerosis Complex Diseases.International journal of genomics · 2026Article
- Comprehensive analysis of non-synonymous single-nucleotide polymorphism of human TSC1 and TSC2 genes: An in silico approach.PloS one · 2026Article
- Structure and mechanism of the RalGAP tumor suppressor complex.Nature communications · 2025Article
- Evolution of growth factor signaling to the TSC complex to regulate mTORC1.Science signaling · 2025Review
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- New insights into tuberous sclerosis complex: from structure to pathogenesis.Frontiers in cell and developmental biology · 2025Review
- Structure of the human TSC:WIPI3 lysosomal recruitment complex.Science advances · 2024Article
- Review
- Design of negative-regulating proteins of Rheb/mTORC1 with much-reduced sizes of the tuberous sclerosis protein complex.Protein science : a publication of the Protein Society · 2023Article
- Targeting the biology of aging with mTOR inhibitors.Nature aging · 2023Review
- Tuberous sclerosis complex is associated with a novel human tauopathy.Acta neuropathologica · 2023Article
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy.Cancers · 2022Review
- Structural insights into TSC complex assembly and GAP activity on Rheb.Nature communications · 2021Article
- The TSC Complex-mTORC1 Axis: From Lysosomes to Stress Granules and Back.Frontiers in cell and developmental biology · 2021Review
- mTORC1 Crosstalk With Stress Granules in Aging and Age-Related Diseases.Frontiers in aging · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The Tuberous Sclerosis Complex (TSC) protein complex (TSCC), comprising TSC1, TSC2, and TBC1D7, is widely recognised as a key integration hub for cell growth and intracellular stress signals upstream of the mammalian target of rapamycin complex 1 (mTORC1). The TSCC negatively regulates mTORC1 by acting as a GTPase-activating protein (GAP) towards the small GTPase Rheb. Both human TSC1 and TSC2 are important tumour suppressors, and mutations in them underlie the disease tuberous sclerosis. We used single-particle cryo-EM to reveal the organisation and architecture of the complete human TSCC. We show that TSCC forms an elongated scorpion-like structure, consisting of a central "body", with a "pincer" and a "tail" at the respective ends. The "body" is composed of a flexible TSC2 HEAT repeat dimer, along the surface of which runs the TSC1 coiled-coil backbone, breaking the symmetry of the dimer. Each end of the body is structurally distinct, representing the N- and C-termini of TSC1; a "pincer" is formed by the highly flexible N-terminal TSC1 core domains and a barbed "tail" makes up the TSC1 coiled-coil-TBC1D7 junction. The TSC2 GAP domain is found abutting the centre of the body on each side of the dimerisation interface, poised to bind a pair of Rheb molecules at a similar separation to the pair in activated mTORC1. Our architectural dissection reveals the mode of association and topology of the complex, casts light on the recruitment of Rheb to the TSCC, and also hints at functional higher order oligomerisation, which has previously been predicted to be important for Rheb-signalling suppression.
Indexed as
Identifiers
What OpenQuestion holds
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.