Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway

Saxton RA, Knockenhauer KE, Wolfson RL, Chantranupong L, Pacold ME, Wang T, Schwartz TU, Sabatini DM · 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

ShowHide

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 type	5 - Mechanistic / In Vitro
Model system	Human cell lines (crystal structure)
Journal	Science
Year	2015
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.aad2087 · PMID 26586190 · Free full text (PMC4698039)

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 (crystal structure of Sestrin2-leucine)
Target	Sestrin2 / leucine / GATOR2 / mTORC1
Model	Human cell lines (crystal structure)
Effect	Structure of Sestrin2 bound to leucine reveals the leucine-sensing mechanism for the mTORC1 pathway

In the Atlas

Links in the pathway map

Supports Leucine inhibits Sestrin2

Open questions that cite this study

Cited as supporting evidence for the open question Sensor-selective geroprotection without the metabolic penalty.

Cite this paper

ShowHide

Saxton, R. A., Knockenhauer, K. E., Wolfson, R. L., Chantranupong, L., Pacold, M. E., Wang, T., Schwartz, T. U., & Sabatini, D. M. (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 Knockenhauer, K. E. and Wolfson, R. L. and Chantranupong, L. and Pacold, M. E. and Wang, T. and Schwartz, T. U. and Sabatini, D. M.},
  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}
}

Was this page useful?