Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP

Choi J, Chen J, Schreiber SL, Clardy J · 1996 · Science · Atlas ID CHO1996

What this study shows

The crystal structure that showed HOW rapamycin works at the atomic level: one rapamycin molecule glues two proteins together - FKBP12 and mTOR's FRB domain - by plugging into two hydrophobic pockets at once. A textbook example of a small molecule acting as 'molecular glue' to force protein dimerization.

Abstract

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Rapamycin, a potent immunosuppressive agent, binds two proteins: the FK506-binding protein (FKBP12) and the FKBP-rapamycin-associated protein (FRAP). A crystal structure of the ternary complex of human FKBP12, rapamycin, and the FKBP12-rapamycin-binding (FRB) domain of human FRAP at a resolution of 2.7 angstroms revealed the two proteins bound together as a result of the ability of rapamycin to occupy two different hydrophobic binding pockets simultaneously. The structure shows extensive interactions between rapamycin and both proteins, but fewer interactions between the proteins.

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	Science
Year	1996
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.273.5272.239 · PMID 8662507

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	FKBP12 / rapamycin / FRAP (FRB domain)
Model	X-ray crystallography
Effect	2.7-Å ternary structure of FKBP12-rapamycin bound to the FRB domain of human FRAP/mTOR

In the Atlas

Links in the pathway map

Supports Rapamycin binds FKBP12
Supports Rapamycin inhibits mTORC1

Learn the biology

Want to understand the biology behind this study? → Challenge 02: Why rapamycin does not switch mTORC1 off

Cite this paper

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Choi, J., Chen, J., Schreiber, S. L., & Clardy, J. (1996). Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science. https://doi.org/10.1126/science.273.5272.239

@article{CHO1996,
  author       = {Choi, J. and Chen, J. and Schreiber, S. L. and Clardy, J.},
  title        = {{Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP}},
  journal      = {Science},
  year         = {1996},
  doi          = {10.1126/science.273.5272.239},
  note         = {PMID: 8662507},
}

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 CHO1996) [Data set]. https://mtor-atlas.org/study/CHO1996/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_CHO1996,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record CHO1996},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/CHO1996/},
  doi          = {10.5281/zenodo.22059963}
}

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