Structure study of osteostatin PTHrP[Thr107](107-139).
The structure of chicken osteostatin or parathyroid hormone-related protein (PTHrP) (residues 107-139) containing an Ala/Thr substitution at the N-terminus was studied using two-dimensional proton NMR spectroscopy in an aqueous environment. Osteostatin is a separate circulating domain responsible for a range of activities related to the modulation of bone formation as well as keratinocyte proliferation. Anti-mitogenic properties of osteostatin have been detected in breast cancer cells and cytosolic calcium is used by osteostatin to signal in some neurons through a non-PTH receptor, unlike the separate circulating N-terminal domain. A structural basis for the activity is presented with particular emphasis given to the conformation of the bioactive segment 107-111, forming part of a finger-like projection capable of binding to the non-PTH receptor both in the presence and absence of the remainder of the molecule which appears simply to act as a largely globular carrier.
Cuthbertson
R M
RM
Institute for Biomedical Research and Department of Anatomy and Histology, University of Sydney, Sydney, NSW 2006, Australia.
Kemp
B E
BE
Barden
J A
JA
D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000737:chemistry*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry*
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; C120229:parathyroid hormone-related protein (107-139)amide