title: Structural plasticity of the cellular prion protein and implications in health and disease.
abstract: Two lines of transgenic mice expressing mouse/elk and mouse/horse prion protein (PrP) hybrids, which both form a well-structured β2-α2 loop in the NMR structures at 20 °C termed rigid-loop cellular prion proteins (RL-PrP(C)), presented with accumulation of the aggregated scrapie form of PrP in brain tissue, and the mouse/elk hybrid has also been shown to develop a spontaneous transmissible spongiform encephalopathy. Independently, there is in vitro evidence for correlations between the amino acid sequence in the β2-α2 loop and the propensity for conformational transitions to disease-related forms of PrP. To further contribute to the structural basis for these observations, this paper presents a detailed characterization of RL-PrP(C) conformations in solution. A dynamic local conformational polymorphism involving the β2-α2 loop was found to be evolutionarily preserved among all mammalian species, including those species for which the WT PrP forms an RL-PrP(C). The interconversion between two ensembles of PrP(C) conformers that contain, respectively, a 310-helix turn or a type I β-turn structure of the β2-α2 loop, exposes two different surface epitopes, which are analyzed for their possible roles in the still evasive function of PrP(C) in healthy organisms and/or at the onset of a transmissible spongiform encephalopathy.
authors: Institute of Molecular Biology and Biophysics, Eidgenössiche Technische Hochschule Zurich, CH-8093 Zurich, Switzerland.
authors: Barbara
authors: B
authors: Christen
authors: Fred F
authors: FF
authors: Damberger
authors: Daniel R
authors: DR
authors: Pérez
authors: Simone
authors: S
authors: Hornemann
authors: Kurt
authors: K
authors: Wüthrich
mesh_terms: D000818:Animals; D001921:Brain; D001923:Brain Chemistry; D003670:Deer; D006736:Horses; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases; D017433:Protein Structure, Secondary
chemical_list: D018621:PrPC Proteins
keywords: NMR line shape analysis; conformational equilibrium; prion protein stability; protein dynamics
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