Evidence map›Paper›PMID 31601708›Full record

ArticleScience (New York, N.Y.)2019

Structural basis for the docking of mTORC1 on the lysosomal surface.

Kacper B Rogala, Xin Gu, Jibril F Kedir, Monther Abu-Remaileh, Laura F Bianchi, Alexia M S Bottino, Rikke Dueholm, Anna Niehaus, Daan Overwijn, Ange-Célia Priso Fils and 5 more

Open access · greenAbstract readVideo-Audio Media
In one paragraph

Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed
12.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

126 citing papers in PubMed, 217 citations in OpenAlex.

  1. Review
  2. RRAGD p.(Ser76Leu) Variant Causes Dysregulated Expression of Muscle Development and Cytoskeleton Genes in Cardiomyocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Architecture of the human KICSTOR and GATOR1-KICSTOR complexes.Nature structural & molecular biology · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. 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 · 2025
    Article
  17. Article
  18. Article
  19. NovelKidney international reports · 2025
    Article
  20. Review

66 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Kacper B RogalaWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0001-5997-7770
Xin GuWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-3393-6927
Jibril F KedirWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-1565-9049
Monther Abu-RemailehWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0003-3772-0477
Laura F BianchiWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Alexia M S BottinoWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0001-7097-9697
Rikke DueholmWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-8263-7421
Anna NiehausWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Daan OverwijnWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Ange-Célia Priso FilsWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-5987-9123
Sherry X ZhouWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-8390-099X
Daniel LearyBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.ORCID 0000-0002-9480-2973
Nouf N LaqtomWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.ORCID 0000-0002-0167-2656
Edward J BrignoleDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0002-4285-6128
David M SabatiniWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. sabatini@wi.mit.edu.ORCID 0000-0002-1446-7256
Whitehead Institute for Biomedical Research · USBroad Institute · USMassachusetts Institute of Technology · US

Funding

PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Regulation of the mTOR Pathway By NutrientsR01CA103866 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2004 to 2021
$7.0M
Cell Growth Signaling in Cancer DevelopmentR01CA129105 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2008 to 2021
$5.9M
Novel Components of the mTORC1 and mTORC2 PathwaysR37AI047389 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI SABATINI, DAVID M. · 2010 to 2019
$4.8M
Regulation by mTORC1 of the lysosomal efflux of essential amino acidsF30CA236179 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KEDIR, JIBRIL · 2019 to 2023
$238k
Howard Hughes Medical InstituteNCI NIH HHS F30 CA236179NCI NIH HHS R01 CA103866NCI NIH HHS R01 CA129105NIAID NIH HHS R37 AI047389NIGMS NIH HHS T32 GM007287
6 · The paper itself

Abstract

The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase regulates growth in response to nutrients and growth factors. Nutrients promote its translocation to the lysosomal surface, where its Raptor subunit interacts with the Rag guanosine triphosphatase (GTPase)-Ragulator complex. Nutrients switch the heterodimeric Rag GTPases among four different nucleotide-binding states, only one of which (RagA/B•GTP-RagC/D•GDP) permits mTORC1 association. We used cryo-electron microscopy to determine the structure of the supercomplex of Raptor with Rag-Ragulator at a resolution of 3.2 angstroms. Our findings indicate that the Raptor α-solenoid directly detects the nucleotide state of RagA while the Raptor "claw" threads between the GTPase domains to detect that of RagC. Mutations that disrupted Rag-Raptor binding inhibited mTORC1 lysosomal localization and signaling. By comparison with a structure of mTORC1 bound to its activator Rheb, we developed a model of active mTORC1 docked on the lysosome.

Indexed as

Cryoelectron MicroscopyHumansLysosomesMechanistic Target of Rapamycin Complex 1Molecular Docking SimulationMonomeric GTP-Binding ProteinsProtein Structure, QuaternaryRegulatory-Associated Protein of mTORSignal TransductionMechanistic Target of Rapamycin Complex 1Monomeric GTP-Binding ProteinsRegulatory-Associated Protein of mTORRPTOR protein, humanRRAGA protein, humanRRAGC protein, human

Identifiers

PMID31601708
PMCPMC7176403
OpenAlexW2979459757

What OpenQuestion holds

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Registered trials

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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.