Understanding the Physical Interactions in the FGF21/FGFR/β‐Klotho Complex: Structural Requirements and Implications in FGF21 Signaling

The endocrine fibroblast growth factor 21 (FGF21) requires both fibroblast growth factor receptor (FGFR) and β‐Klotho for signaling. In this study, we sought to understand the inter‐molecular physical interactions in the FGF21/FGFR/β‐Klotho complex by deleting key regions in FGFR1c or FGF21. Deletion of the D1 and the D1‐D2 linker (the D1/linker region) from FGFR1c led to β‐Klotho‐independent receptor activation by FGF21, suggesting that there...