Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40

Yang H, Jiang X, Li B, Yang HJ, Miller M, Yang A, Dhar A, Pavletich NP · 2017 · Nature · Atlas ID YAN2017

What this study shows

Structures reveal how RHEB allosterically activates and PRAS40 inhibits mTORC1.

Abstract

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The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 angstrom cryo-electron microscopy structure of mTORC1 and the 3.4 angstrom structure of activated RHEB-mTORC1.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Cryo-EM structure) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Cryo-EM structure
Journal	Nature
Year	2017
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/nature25023 · PMID 29236692 · Free full text (PMC5750076)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Structural (cryo-EM)
Target	mTORC1 / RHEB / PRAS40
Model	Cryo-EM structure
Effect	Structures reveal how RHEB allosterically activates mTORC1 and how PRAS40 inhibits it

In the Atlas

Links in the pathway map

Supports PRAS40 inhibits mTORC1
Supports Rheb activates mTORC1

Cite this paper

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Yang, H., Jiang, X., Li, B., Yang, H. J., Miller, M., Yang, A., Dhar, A., & Pavletich, N. P. (2017). Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. Nature. https://doi.org/10.1038/nature25023

@article{YAN2017,
  author       = {Yang, H. and Jiang, X. and Li, B. and Yang, H. J. and Miller, M. and Yang, A. and Dhar, A. and Pavletich, N. P.},
  title        = {{Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40}},
  journal      = {Nature},
  year         = {2017},
  doi          = {10.1038/nature25023},
  note         = {PMID: 29236692},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record YAN2017) [Data set]. https://mtor-atlas.org/study/YAN2017/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_YAN2017,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record YAN2017},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/YAN2017/},
  doi          = {10.5281/zenodo.22059963}
}

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