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Related Experiment Video

Updated: Jul 15, 2025

Affinity Labeling Detection of Endogenous Receptors from Zebrafish Embryos

Affinity Labeling Detection of Endogenous Receptors from Zebrafish Embryos

Published on: August 31, 2016

Structural asymmetry in FGF23 signaling.

Shih-Hsien Liu¹, Zhousheng Xiao², Jeremy C Smith¹

¹UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA.

Trends in Pharmacological Sciences

|October 1, 2023

Summary

Researchers visualized fibroblast growth factor 23 (FGF23) signaling complexes using cryo-EM. The asymmetric structures reveal new insights into FGF23

Keywords:

FGF signaling FGF23 FGFR drug discovery α-Klotho

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Last Updated: Jul 15, 2025

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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

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Published on: January 31, 2025

Area of Science:

Structural Biology
Endocrinology
Biochemistry

Background:

Fibroblast growth factor 23 (FGF23) is a key endocrine hormone regulating phosphate and vitamin D metabolism.
Dysregulation of FGF23 signaling is implicated in various diseases, including kidney disease and tumoral calcinosis.
Understanding the molecular interactions of FGF23 is crucial for therapeutic interventions.

Purpose of the Study:

To determine the high-resolution structures of FGF23 signaling complexes.
To elucidate the molecular mechanisms underlying FGF23 receptor activation.
To provide a structural basis for the development of novel therapeutics targeting FGF23 signaling.

Main Methods:

Cryogenic electron microscopy (cryo-EM) was employed to resolve the structures.
Purified recombinant proteins of FGF23, FGFR, α-Klotho, and heparin sulfate were used.
Computational modeling and structural analysis were performed.

Main Results:

Asymmetric structures of the FGF23-FGFR-α-Klotho-heparin sulfate signaling complex were determined.
Key interaction interfaces and conformational states were identified.
Structural heterogeneity suggests dynamic aspects of complex formation.

Conclusions:

The derived cryo-EM structures provide unprecedented atomic-level detail of the FGF23 signaling machinery.
The observed asymmetry raises important questions about the in vivo functional mechanisms.
These findings will facilitate structure-based drug design for modulating FGF23 signaling pathways.