Oliver's mTOR Atlas Evidence Platform
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Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway

Saxton RA, Wolfson RL, Sabatini DM et al. · 2015 · Science · Atlas ID SAX2015

What this study shows

Solves the crystal structure of Sestrin2 bound to leucine, revealing the molecular pocket that lets it act as mTORC1's dedicated leucine sensor.

Abstract

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Eukaryotic cells coordinate growth with the availability of nutrients through the mechanistic target of rapamycin complex 1 (mTORC1), a master growth regulator. Leucine is of particular importance and activates mTORC1 via the Rag guanosine triphosphatases and their regulators GATOR1 and GATOR2. Sestrin2 interacts with GATOR2 and is a leucine sensor. Here we present the 2.7 angstrom crystal structure of Sestrin2 in complex with leucine. Leucine binds through a single pocket that coordinates its charged functional groups and confers specificity for the hydrophobic side chain.

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: Human cell lines (crystal 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 type5 - Mechanistic / In Vitro
Model systemHuman cell lines (crystal structure)
JournalScience
Year2015
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1126/science.aad2087 · PMID 26586190 · Free full text (PMC4698039)

Extracted findings

InterventionStructural (crystal structure of Sestrin2-leucine)
TargetSestrin2 / leucine / GATOR2 / mTORC1
ModelHuman cell lines (crystal structure)
EffectStructure of Sestrin2 bound to leucine reveals the leucine-sensing mechanism for the mTORC1 pathway

In the Atlas

Related topics

LeucineSestrin2mTORC1

Open questions that cite this study

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Cite this paper

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Saxton, R. A., et al. (2015). Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science. https://doi.org/10.1126/science.aad2087

@article{SAX2015,
  author       = {Saxton, R. A. and Wolfson, R. L. and Sabatini, D. M. and others},
  title        = {{Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway}},
  journal      = {Science},
  year         = {2015},
  doi          = {10.1126/science.aad2087},
  note         = {PMID: 26586190},
}

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 SAX2015) [Data set]. https://mtor-atlas.org/study/SAX2015/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SAX2015,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SAX2015},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SAX2015/},
  doi          = {10.5281/zenodo.22059963}
}