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More About Rapamycin Superactivates a Protein

In “Using Small Molecules to Modulate a Protein” animation, a small molecule was shown inactivating a protein. Small molecules can also superactivate a protein, enhancing its normal property, or endowing it with a completely new property. FKBP12 (in blue) and FRAP (purple) are two proteins found in human cells. Normally they do not interact with each other. Rapamycin (gold) is a small molecule with a high affinity for FKBP12. When it binds to FKBP12, it creates a composite surface which in turn binds to FRAP. In effect, FKBP12 is ‘super-activated’ to have a new property.

The complex of FKBP12-rapamycin-FRAP has important physiological implications, because FRAP is part of the glucose sensing protein network.

Rapamycin Background

Rapamycin is a molecule with an antibiotic property that was isolated from a soil-dwelling microorganism sampled on Easter Island. The name derives from the native name for the island, Rapa Nui. Later research showed that the molecule has immunosuppressive properties and is used in many clinical applications, including suppressing the host response to reject transplanted tissue.

Recently, it has been discovered that rapamycin also interacts with a protein called FKBP12. When rapamycin binds to FKBP12, the combination can form a complex with FRAP protein. FRAP is part of the glucose sensing network. The FKBP12-rapamycin-FRAP complex interferes with the normal operation of this network, and induces Type II diabetes in patients taking rapamycin as an immunosuppressive drug. Patients who have developed this condition have shown recovery from the diabetic condition after rapamycin was temporarily switched with another immunosuppressive drug.


HHMI's 2002 Holiday Lectures on Science "Scanning Life's Matrix: Genes, Proteins and Small Molecules"

Rapamycin Teaching Tips

The animations in this section have a wide variety of classroom applications. Use the tips below to get started but look for more specific teaching tips in the near future. Please tell us how you are using the animations in your classroom by sending e-mail to biointeractive@hhmi.org.

  1. Use the animations to make abstract scientific ideas visible and concrete.

  2. Explain important scientific principles through the animations. For example, the biological clocks animations can be used to demonstrate the fundamentals of transcription and translation.

  3. Make sure that students learn the material by repeating sections of the animations as often as you think necessary to reinforce underlying scientific principles. You can start, restart, and play back sections of the animations.

  4. Urge students to use the animations in accordance with their own learning styles. Students who are more visually oriented can watch the animations first and read the text later, while others might prefer to read the explanations first and then view the graphics.

  5. Incorporate the animations into Web-based learning modules that you create to supplement your classroom curricula.

  6. Encourage students to incorporate the animations into their own Web-based projects.

Rapamycin Credits

Director: Dennis Liu, Ph.D.

Scientific Direction: Stuart L. Schreiber, Ph.D.

Scientific Content: Satoshi Amagai, Ph.D.

Animator: Eric Keller

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