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
✍ Scribed by Aizhuo Liu; Roland Riek; Ralph Zahn; Simone Hornemann; Rudi Glockshuber; Kurt Wüthrich
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 1999
- Tongue
- English
- Weight
- 169 KB
- Volume
- 51
- Category
- Article
- ISSN
- 0006-3525
No coin nor oath required. For personal study only.
✦ Synopsis
Transmissible spongiform encephalopathies (TSE) or "prion diseases" have been related to the "protein-only hypothesis", which suggests that the "scrapie form (PrP Sc )" of the prion protein (PrP) is the TSE infectious agent. The nmr structure of the ubiquitous benign cellular form of PrP (PrP C ) consists of a globular domain of residues 126 -231 with three ␣-helices and a short -sheet, and a flexible extended "tail" of residues 23-125. The peptide segment of helix 1 has been implicated in various stages of hypothetical pathways to prion pathology on the basis of the protein-only idea, including that it takes part in the conformation change that leads from PrP C to PrP Sc . In this paper we describe solution nmr and circular dichroism studies of the synthetic hexadecapeptide mPrP(143-158), with the sequence H-NDWEDRYYRENMYRYP-NH 2 , where the bold letters represent the segment that forms helix 1 in murine PrP C . In both H 2 O and a 1:1 mixture of H 2 O and trifluoroethanol this polypeptide segment shows high helix propensity, which is a key issue in discussions on potential roles of this molecular region in conformational transitions of PrP.