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-ter minus was studied using two-dimensional proton NMR spectroscopy in an aqueo us environment. Osteostatin is a separate circulating domain responsible fo r a range of activities related to the modulation of bone formation as well as keratinocyte proliferation. Anti-mitogenic properties of osteostatin ha ve been detected in breast cancer cells and cytosolic calcium is used by os teostatin 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 bio active 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 re mainder of the molecule which appears simply to act as a largely globular c arrier. (C) 1999 Elsevier Science B.V. All rights reserved.