Fig. 1.

Structure of the FGF23-FGFR-Klotho ternary complex¹⁷⁾

The extracellular domain of Klotho protein is composed of two internal repeats, termed KL1 and KL2 domains, with homology to family 1 glycosidases. KL2 domain sends out the receptor binding arm (RBA), which has an intrinsically disordered structure and interacts with the D3 domain of fibroblast growth factor receptor (FGFR). Once the RBA binds to the D3 domain of FGFR, the binding pocket for FGF23 is generated. Formation of the ternary complex composed of FGFR, FGF23, and Klotho is required for activation of the canonical FGF signaling. Modified from Refs. 15 and 17.