Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

A ligand-reversible dimerization system for controlling protein-protein interactions.

C T Rollins1, V M Rivera, D N Woolfson

  • 1ARIAD Gene Therapeutics, Inc., 26 Landsdowne Street, Cambridge, MA 02139, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 15, 2000
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Labile assembly of a tardigrade protein induces biostasis.

Protein science : a publication of the Protein Society·2024
Same author

Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly.

Nature communications·2023
Same author

Decreased neonatal morbidity in 'stomach-down' left congenital diaphragmatic hernia: implications of prenatal ultrasound diagnosis for counseling and postnatal management.

Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology·2021
Same author

Variability of nonpathogenic influenza virus H5N3 under immune pressure.

Acta virologica·2020
Same author

A standardized head-fixation system for performing large-scale, in vivo physiological recordings in mice.

Journal of neuroscience methods·2020
Same author

[Therapeutic attitudes towards multiple sclerosis in Central America and the Caribbean facing the SARS-CoV-2 pandemia].

Neurologia·2020
Same journal

Chemotactic self-organization captures the dynamics of mammalian hair follicle patterning.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Tomographic imaging of superconducting order using particle-hole interference.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Inhibitory potential of autologous neutralizing antibodies sets quantitative limits on the rebound-competent HIV-1 reservoir.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Inferring epidemiological parameters under an infectious phylogeography model with visitor dynamics.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Analytical modeling for suction cup designs for skin-interfaced wearable devices.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Improving cell-free metabolism through direct integration of artificial respiratory chains.

Proceedings of the National Academy of Sciences of the United States of America·2026
See all related articles

Researchers engineered a mutant FKBP protein that forms reversible dimers. This discovery enables a novel "reverse dimerization" system for controlling cellular processes, offering a powerful tool for molecular regulation.

Area of Science:

  • Molecular Biology
  • Protein Engineering
  • Biochemistry

Background:

  • Chemically induced dimerization is a common method for controlling intracellular processes.
  • FK506-binding protein (FKBP) domains are typically fused to signaling domains and crosslinked with bivalent ligands.

Purpose of the Study:

  • To engineer a novel FKBP-based system for controlling intracellular events.
  • To investigate the properties of a mutated FKBP protein with altered dimerization behavior.

Main Methods:

  • Protein engineering of human FKBP, introducing a Phe-36 to Met mutation.
  • Utilizing yeast two-hybrid assays, gel filtration, analytical ultracentrifugation, and X-ray crystallography.
  • Developing and testing a "reverse dimerization" system using F(M) fusion proteins.

Related Experiment Videos

Main Results:

  • A single point mutation (Phe-36 --> Met) converted monomeric FKBP into a ligand-reversible homodimer (F(M)).
  • The F(M) mutant forms stable homodimers with micromolar affinity, dissociable by monomeric ligands.
  • Demonstrated rapid and reversible aggregation of F(M) fusion proteins in cellular compartments and transcription control.

Conclusions:

  • The F(M) mutant FKBP enables a "reverse dimerization" system where association is the default state, reversed by ligand addition.
  • Reiterated F(M) domains serve as conditional aggregation domains (CADs) for precise control of intracellular events.
  • Dimerization appears to be an inherent property of the FKBP fold, modulated by subtle structural changes.