The structure of human parathyroid hormone-related protein(1-34) in near-physiological solution.
Parathyroid hormone-related protein plays a major role in the pathogenesis of humoral hypercalcemia of malignancy. Under normal physiological conditions, parathyroid hormone-related protein is produced in a wide variety of tissues and acts in an autocrine or paracrine fashion. Parathyroid hormone-related protein and parathyroid hormone bind to and activate the same G-protein-coupled receptor. Here we present the structure of the biologically active NH2-terminal domain of human parathyroid hormone-related protein(1-34) in near-physiological solution in the absence of crowding reagents as determined by two-dimensional proton magnetic resonance spectroscopy. An improved strategy for structure calculation revealed the presence of two helices, His-5-Leu-8 and Gln-16-Leu-27, connected by a flexible linker. The parathyroid hormone-related protein(1-34) structure and the structure of human parathyroid hormone(1-37) as well as human parathyroid hormone(1-34) are highly similar, except for the well defined turn, His-14-Ser-17, present in parathyroid hormone. Thus, the similarity of the binding affinities of parathyroid hormone and parathyroid hormone-related protein to their common receptor may be based on their structural similarity.
Lehrstuhl für Biopolymere, Universität Bayreuth, Germany.
M
M
Weidler
U C
UC
Marx
G
G
Seidel
W
W
Schäfer
E
E
Hoffmann
A
A
Esswein
P
P
Rösch
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000737:chemistry; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34)