NMR structure of a minimum activity domain of human parathyroid peptide hormone: structural origin of receptor activation. |
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| Authors: | J Jung S-K Lim Y Kim W Lee |
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| Affiliation: | Department of Biochemistry and Protein Network Research Center, College of Science, Yonsei University, Shinchon-Dong, Seoul, Korea. |
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| Abstract: | 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. |
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