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

FGFR3 dimer stabilization due to a single amino acid pathogenic mutation.

Edwin Li1, Min You, Kalina Hristova

  • 1Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.

Journal of Molecular Biology
|December 31, 2005
PubMed
Summary

Pathogenic mutations in receptor tyrosine kinase (RTK) transmembrane domains can stabilize receptor dimers. This study quantifies the free energy change for a specific mutation, revealing its role in promoting unregulated signaling.

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

Management of Type 2 Diabetes Mellitus: Targeting Gut Microbiome Therapy.

The American journal of Chinese medicine·2026
Same author

Conceptualization, Contexts, and Measurement of Nursing Theoretical Literacy: Protocol for a Scoping Review.

JMIR research protocols·2026
Same author

Development and Optimization of CRISPR/Cas9-Assisted Recombineering in <i>Escherichia albertii</i>.

microPublication biology·2026
Same author

Conceptualization, Contexts, and Measurement of Nursing Theoretical Literacy: Protocol for a Scoping Review.

JMIR research protocols·2026
Same author

Attitudes and participation in fall risk management: A tripartite, multicenter cross-sectional study of physicians, nurses, and patients.

PloS one·2026
Same author

An Oral Mucosa-Inspired Wet-Adhesion Janus Hydrogel With Asymmetric Bifunctionalities of Antifouling/Antioxidant for Treating Oral Ulcer in Diabetes.

Small (Weinheim an der Bergstrasse, Germany)·2026

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Mutations in transmembrane (TM) domains of receptor tyrosine kinases (RTKs) are linked to diseases by promoting unregulated signaling.
  • The energetic basis for how these mutations stabilize RTK dimers in cell membranes remains unclear.

Purpose of the Study:

  • To determine the free energy of dimerization for wild-type and mutant fibroblast growth factor receptor 3 (FGFR3) TM domain in lipid bilayers.
  • To investigate the mechanism of dimer stabilization by a pathogenic mutation (Ala391-->Glu) in FGFR3.

Main Methods:

  • Utilizing Förster resonance energy transfer (FRET) to measure the free energy of dimerization.
  • Employing lipid bilayers to mimic the native membrane environment for the FGFR3 TM domain.

Related Experiment Videos

Main Results:

  • The Ala391-->Glu mutation in FGFR3 TM domain resulted in a measured change in free energy of dimerization of -1.3 kcal/mol.
  • Hydrogen bonding between Glu391 and an adjacent helix in the dimer interface was identified as a feasible stabilization mechanism.
  • This quantitative measurement is the first of its kind for mutant RTK stabilization in a membrane.

Conclusions:

  • The modest free energy change associated with the pathogenic mutation significantly increases receptor dimer fraction.
  • This stabilization profoundly impacts RTK-mediated signal transduction, offering insights into disease mechanisms.
  • Findings provide a quantitative energetic basis for pathological phenotypes driven by RTK TM domain mutations.