Evidence map›Paper›PMID 31704029›Full record

ArticleCell2019

Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex.

Kuang Shen, Kacper B Rogala, Hui-Ting Chou, Rick K Huang, Zhiheng Yu, David M Sabatini

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
7.5field-weighted citation impact, top 2% 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

89 citing papers in PubMed, 134 citations in OpenAlex.

  1. Article
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  7. Genome-wide single-cell perturbation screens with VIPerturb-seq.bioRxiv : the preprint server for biology · 2026
    Article
  8. Review
  9. Review
  10. 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
  11. Article
  12. Article
  13. Article
  14. Review
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  16. Review
  17. 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 · 2024
    Article
  18. Review
  19. Article
  20. Review

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Kuang ShenWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 455 Main Street, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA; Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, 01605, USA.
Kacper B RogalaWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 455 Main Street, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA.
Hui-Ting ChouHoward Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
Rick K HuangHoward Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
Zhiheng YuHoward Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA. Electronic address: yuz@janelia.hhmi.org.
David M SabatiniWhitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 455 Main Street, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: sabatini@wi.mit.edu.
Broad Institute · USHoward Hughes Medical Institute · USJanelia Research Campus · USWhitehead Institute for Biomedical Research · US

Funding

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
Spatial and temporal regulation of nutrient sensingR35GM146824 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Kuang Shen · 2022 to 2026
$2.2M
A Molecular Study of Rag GTPase-Dependent Amino Acid SensingK22CA241362 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SHEN, KUANG · 2020 to 2022
$612k
Howard Hughes Medical InstituteNCI NIH HHS K22 CA241362NCI NIH HHS R01 CA103866NCI NIH HHS R01 CA129105NIAID NIH HHS R37 AI047389NIGMS NIH HHS R35 GM146824
6 · The paper itself

Abstract

mTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN-FNIP2, is a GTPase activating protein (GAP) for RagC/D, but despite its important role, how it activates the Rag GTPase heterodimer remains unknown. We used cryo-EM to determine the structure of FLCN-FNIP2 in a complex with the Rag GTPases and Ragulator. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. The Longin domains heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, while the DENN domains interact at the distal end of the structure. Biochemical analyses reveal a conserved arginine on FLCN as the catalytic arginine finger and lead us to interpret our structure as an on-pathway intermediate. These data reveal features of a GAP-GTPase interaction and the structure of a critical component of the nutrient-sensing mTORC1 pathway.

Indexed as

Cryoelectron MicroscopyArginineBiocatalysisCarrier ProteinsGTPase-Activating ProteinsHEK293 CellsHumansHydrolysisModels, MolecularMonomeric GTP-Binding ProteinsMultiprotein ComplexesProtein ConformationProtein MultimerizationProto-Oncogene ProteinsTumor Suppressor ProteinsArginineCarrier ProteinsFLCN protein, humanFNIP2 protein, humanGTPase-Activating ProteinsMonomeric GTP-Binding ProteinsMultiprotein ComplexesProto-Oncogene ProteinsTumor Suppressor Proteins

Identifiers

PMID31704029
PMCPMC7008705
OpenAlexW2989525167

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.