mTOR kinase structure, mechanism and regulation

Yang H, Rudge DG, Koos JD, Vaidialingam B, Yang HJ, Pavletich NP · 2013 · Nature · Atlas ID YAN2013

What this study shows

Solved the crystal structure of the mTOR kinase itself. Revealed why the active site is so hard to reach - it sits in a deep recess guarded by the FRB domain, which acts as a 'gatekeeper' letting substrates in. This structure explains at the atomic level exactly how FKBP12-rapamycin blocks access, and why activating cancer mutations cluster where they do.

Abstract

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The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13 protein 8 (mLST8) with an ATP transition state mimic and with ATP-site inhibitors. The structures reveal an intrinsically active kinase conformation, with catalytic residues and a catalytic mechanism remarkably similar to canonical protein kinases.

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: X-ray crystallography (structural biology)) 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	X-ray crystallography (structural biology)
Journal	Nature
Year	2013
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/nature12122 · PMID 23636326 · Free full text (PMC4512754)

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 (X-ray crystallography)
Target	mTOR / mLST8
Model	X-ray crystallography
Effect	Co-crystal structures reveal mTOR's intrinsically active kinase and how ATP-site inhibitors bind

In the Atlas

Cite this paper

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Yang, H., Rudge, D. G., Koos, J. D., Vaidialingam, B., Yang, H. J., & Pavletich, N. P. (2013). mTOR kinase structure, mechanism and regulation. Nature. https://doi.org/10.1038/nature12122

@article{YAN2013,
  author       = {Yang, H. and Rudge, D. G. and Koos, J. D. and Vaidialingam, B. and Yang, H. J. and Pavletich, N. P.},
  title        = {{mTOR kinase structure, mechanism and regulation}},
  journal      = {Nature},
  year         = {2013},
  doi          = {10.1038/nature12122},
  note         = {PMID: 23636326},
}

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 YAN2013) [Data set]. https://mtor-atlas.org/study/YAN2013/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_YAN2013,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record YAN2013},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/YAN2013/},
  doi          = {10.5281/zenodo.22059963}
}

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