FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho

Significance FGF23 is a circulating hormone produced in bone tissue that acts in the kidney to increase phosphate excretion and vitamin D metabolism essential for calcium absorption. Mutations that elevate FGF23 abundance cause autosomal dominant hypophosphatemic rickets or tumor-induced osteomalacia. Loss of FGF23, on the other hand, causes increased phosphate levels, such as in familiar tumor calcinosis. Here we show that the region in FGF23...