Peptides and proteins in neurodegenerative disease: Helix propensity of a polypeptide containing helix 1 of the mouse prion protein studied by NMR and CD spectroscopy

: Transmissible spongiform encephalopathies (TSE) or "prion diseases" have been related to the "protein-only hypothesis", which suggests that the "scr apie form (PrPSc)" of the the prion protein (PrP) is the TSE infectious age nt. The nmr structure of the ubiquitous benign cellular form of PrP (PrPC) consists of a globular domain of residues 126-231 with three cu-helices and a short P-sheet, and a flexible extended "tail" of residues 23-125. The pe ptide segment of helix I has been implicated in various stages of hypotheti cal pathways to prion pathology on the basis of the proteim-only idea, incl uding that it takes part in the conformation change that fends from PrPC to PrPSc. in this paper we describe solution nmr and circular dichroism studi es of the synthetic hexadecapeptide mPrP(143-158), with the sequence H-NDWE DRYYRENMYRYP-NH2, where the bold letters represent the segment that forms h elix I in murine PrPC. In both H2O and a 1:1 mixture of H2O and trifluoroet hanol this polypeptide segment shows high helix propensity, which is a key issue in discussions an potential roles of this molecular region in conform ational transitions of PrP. (C) 1999 John Wiley & Sons, Inc.