Evidence map›Paper›PMID 40715445›Full record

ArticleNature structural & molecular biology2025

Structural basis for mTORC1 regulation by the CASTOR1-GATOR2 complex.

Rachel M Jansen, Clément Maghe, Karla Tapia, Selina Wu, Serim Yang, Xuefeng Ren, Roberto Zoncu, James H Hurley

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Rachel M JansenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Clément MagheDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Karla TapiaDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Selina WuDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Serim YangDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0001-1787-2636
Xuefeng RenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-4822-4316
Roberto ZoncuDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. rzoncu@berkeley.edu.ORCID http://orcid.org/0000-0003-1611-1891
James H HurleyDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. jimhurley@berkeley.edu.ORCID http://orcid.org/0000-0001-5054-5445

Funding

Molecular Mechanisms of Organelle-based Metabolic SignalingR35GM149302 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Roberto Zoncu · 2023 to 2026
$2.4M
Molecular and structural mechanisms of mTORC1 regulation in cancerR01CA285366 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI James H Hurley · 2024 to 2026
$1.8M
NCI NIH HHS R01 CA285366NIGMS NIH HHS R35 GM149302
6 · The paper itself

Abstract

Mechanistic target of rapamycin complex 1 (mTORC1) is a nutrient-responsive master regulator of metabolism. Amino acids control the recruitment and activation of mTORC1 at the lysosome through the nucleotide loading state of the heterodimeric Rag GTPases. Under low nutrients, including arginine, the GTPase-activating protein complex GATOR1 promotes GTP hydrolysis on RagA/B, inactivating mTORC1. GATOR1 is regulated by the cage-like GATOR2 complex and cytosolic amino acid sensors. To understand how the arginine sensor CASTOR1 binds to GATOR2 to disinhibit GATOR1 under low cytosolic arginine, we determined the cryo-electron microscopy structure of human GATOR2 bound to CASTOR1 in the absence of arginine. Two MIOS WD40 domain β-propellers of the GATOR2 cage engage with both subunits of a single CASTOR1 homodimer. Each propeller binds to a negatively charged MIOS-binding interface on CASTOR1 that is distal to the arginine pocket. The structure shows how arginine-triggered loop ordering in CASTOR1 blocks the MIOS-binding interface, switches off its binding to GATOR2 and, thus, communicates to downstream mTORC1 activation.

Indexed as

GTPase-Activating ProteinsIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 1ArginineCryoelectron MicroscopyHumansModels, MolecularMonomeric GTP-Binding ProteinsProtein BindingArginineCASTOR1 protein, humanGTPase-Activating ProteinsIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 1Monomeric GTP-Binding ProteinsRRAGC protein, human

Identifiers

PMID40715445
PMCPMC12477443

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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.