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 "scrapie form (PrPSc)" of the prion protein (PrP) is the TSE infectious agent. The nmr structure of the ubiquitous benign cellular form of PrP (PrPC) consists of a globular domain of residues 126-231 with three alpha-helices and a short beta-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 PrPC to PrPSc. In this paper we describe solution nmr and circular dichroism studies of the synthetic hexadecapeptide mPrP(143-158), with the sequence H-NDWEDRYYRENMYRYP-NH2, where the bold letters represent the segment that forms helix 1 in murine PrPC. In both H2O and a 1:1 mixture of H2O 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.
Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule, CH-8093 Zürich, Switzerland.
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A
Liu
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R
Riek
R
R
Zahn
S
S
Hornemann
R
R
Glockshuber
K
K
Wüthrich
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis; D018621:PrPC Proteins / Q000737:chemistry; D018620:PrPSc Proteins / Q000737:chemistry; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D010446:Peptide Fragments; D010455:Peptides; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions; C121119:prion protein (143-158)