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 Ser(3) to Leu(11) 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.
Jung
J
J
Department of Biochemistry and Protein Network Research Center, College of Science, Yonsei University, Shinchon-Dong, Seoul, Korea.
Lim
S-K
SK
Kim
Y
Y
Lee
W
W
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
D010281:Parathyroid Hormone; D018016:Receptors, Parathyroid Hormone