title: CD and NMR studies of prion protein (PrP) helix 1. Novel implications for its role in the PrPC-->PrPSc conversion process.
abstract: The conversion of prion helix 1 from an alpha-helical into an extended conformation is generally assumed to be an essential step in the conversion of the cellular isoform PrPC of the prion protein to the pathogenic isoform PrPSc. Peptides encompassing helix 1 and flanking sequences were analyzed by nuclear magnetic resonance and circular dichroism. Our results indicate a remarkably high instrinsic helix propensity of the helix 1 region. In particular, these peptides retain significant helicity under a wide range of conditions, such as high salt, pH variation, and presence of organic co-solvents. As evidenced by a data base search, the pattern of charged residues present in helix 1 generally favors helical structures over alternative conformations. Because of its high stability against environmental changes, helix 1 is unlikely to be involved in the initial steps of the pathogenic conformational change. Our results implicate that interconversion of helix 1 is rather representing a barrier than a nucleus for the PrPC-->PrPSc conversion.
authors.affiliation: Lehrstuhl für Biopolymere, Universität Bayreuth, 95447 Bayreuth, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Ziegler
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sticht
authors.forename: Ute C
authors.initials: UC
authors.lastname: Marx
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Müller
authors.forename: Paul
authors.initials: P
authors.lastname: Rösch
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwarzinger
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry; D018621:PrPC Proteins / Q000737:chemistry*; D018620:PrPSc Proteins / Q000737:chemistry*; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D012492:Salts / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology; D055672:Static Electricity
chemical_list: D010455:Peptides; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions; D020033:Protein Isoforms; D012492:Salts; D012997:Solvents