Structural asymmetry in FGF23 signaling

Trends Pharmacol Sci. 2023 Dec;44(12):862-864. doi: 10.1016/j.tips.2023.09.005. Epub 2023 Sep 29.

Abstract

Chen et al. have derived cryogenic electron microscopy (cryo-EM) structures of signaling complexes of the endocrine hormone fibroblast growth factor 23 (FGF23) with fibroblast growth factor receptor (FGFR), α-Klotho, and heparin sulfate. These structures are asymmetric, leading to questions concerning in vivo function, and will facilitate structure-based drug design to modulate FGF23 signaling.

Keywords: FGF signaling; FGF23; FGFR; drug discovery; α-Klotho.

MeSH terms

  • Fibroblast Growth Factors* / chemistry
  • Glucuronidase / metabolism
  • Humans
  • Klotho Proteins*
  • Receptors, Fibroblast Growth Factor / metabolism
  • Signal Transduction / physiology

Substances

  • Klotho Proteins
  • Fibroblast Growth Factors
  • Glucuronidase
  • Receptors, Fibroblast Growth Factor