Data di Pubblicazione:
2003
Citazione:
Structural Properties of Gerstmann-Sträussler-Scheinker Disease Amyloid Protein / M. Salmona, M. Morbin, T. Massignan, L. Colombo, G. Mazzoleni, R. Capobianco, L. Diomede, F. Thaler, L. Mollica, G. Musco, J.J. Kourie, O. Bugiani, D. Sharma, H. Inouye, D.A. Kirschner, G. Forloni, F. Tagliavini. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 278:48(2003), pp. 48146-48153.
Abstract:
Prion protein (PrP) amyloid formation is a central feature of genetic and acquired forms of prion disease such as Gerstmann-Sträussler-Scheinker disease (GSS) and variant Creutzfeldt-Jakob disease. The major component of GSS amyloid is a PrP fragment spanning residues ∼82-146. To investigate the determinants of the physicochemical properties of this fragment, we synthesized PrP-(82-146) and variants thereof, including entirely and partially scrambled peptides. PrP-(82-146) readily formed aggregates that were partially resistant to protease digestion. Peptide assemblies consisted of 9.8-nm-diameter fibrils having a parallel cross-β-structure. Second derivative of infrared spectra indicated that PrP-(82-146) aggregates are primarily composed of β-sheet (54%) and turn (24%) which is consistent with their amyloid-like properties. The peptide induced a remarkable increase in plasma membrane microviscosity of primary neurons. Modification of the amino acid sequence 106-126 caused a striking increase in aggregation rate, with formation of large amount of protease-resistant amorphous material and relatively few amyloid fibrils. Alteration of the 127-146 region had even more profound effects, with the inability to generate amyloid fibrils. These data indicate that the intrinsic properties of PrP-(82-146) are dependent upon the integrity of the C-terminal region and account for the massive deposition of PrP amyloid in GSS.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
x-ray-diffraction; human prion protein; scrapie prion; alpha-helices; PRP peptides; in-vitro; fragment; indiana; residues 106-126; fibrilis
Elenco autori:
M. Salmona, M. Morbin, T. Massignan, L. Colombo, G. Mazzoleni, R. Capobianco, L. Diomede, F. Thaler, L. Mollica, G. Musco, J.J. Kourie, O. Bugiani, D. Sharma, H. Inouye, D.A. Kirschner, G. Forloni, F. Tagliavini
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