Structural Basis for Parathyroid Hormone-Related Protein Binding to the Parathyroid Hormone Receptor and Design of Conformation-Selective Peptides

Pioszak, A.A., et al., 284(41), 28382-28391, J Biological Chemistry, 2009

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are two related peptides that control calcium/phosphate homeostasis and bone development, respectively, through activation of the PTH/PTHrP receptor (PTH1R). The Octet system was used to understand these interactions. Isolated PTH1R ECD (residues 23-191) was biotinylated at the N terminus and immobilized on Streptavidin biosensors. The binding of PTH(1-34)NH2 and PTHrP(1-34)NH2 in solution was assessed. Both ligands bind to the PTH1R with similar affinties; however, differences exist in their underlying biochemical mechanisms.

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