NMR structure of a minimum activity domain of human parathyroid peptide hormone: Structural origin of receptor activation

Parathyroid hormone (PTH) which increases osteoblast numbers and bone formation by activating bone-lining cells to osteoblasts plays an important role in calcium and phosphate homeostasis and bone remodeling by activating PTH receptors. To determine the structural origin of a minimum activity domain of hPTH, we initiated a detailed structural determination of the hPTH^H14 in aqueous solution using NMR spectroscopy. Circular dichroism and NMR data demonstrated that hPTH^H14 maintains a typical helical conformation in both membrane-mimicking environments and 30% TFE solution. The solution structure clearly showed that the residues from Ser³ to Leu¹¹ of hPTH^H14 formed a stable helical structure, especially having charged side-chains oriented in opposite directions relative to one another for optimum interaction with the receptor molecule.