Synthetic peptides homologous to prion protein residues 106-147 form amyloid-like fibrils in vitro.

• DOI: 10.1073/pnas.90.20.9678
• Publication Date: 2006-05-31T12:32:55Z
• Authors: F Tagliavini; F Prelli; L Verga; G Giaccone; R Sarma; P Gorevic; B Ghetti; F Passerini; E Ghibaudi; G Forloni
• Keywords: Fibrillogenesis; Amyloid (mycology); PRNP

Gerstmann-Sträussler-Scheinker disease (GSS) is a prion-related encephalopathy pathologically characterized by massive deposition of prion protein (PrP) amyloid in the central nervous system. The major component fibrils isolated from patients Indiana kindred GSS (GSS-Ik) an 11-kDa fragment PrP spanning residues 58 to approximately 150. These carry missense mutation PRNP gene, causing Phe-->Ser substitution at codon 198. We investigated fibrillogenesis vitro using synthetic peptides homologous consecutive segments GSS-Ik (residues 57-64, 89-106, 106-126, and 127-147) as well region with 191-205 181-205, both wild type mutant). Peptide PrP-(106-126) formed straight similar those extracted brains, whereas peptide PrP-(127-147) twisted resembling scrapie-associated subjects transmissible spongiform encephalopathies. Congo red staining x-ray fibril diffraction showed that had tinctorial conformational properties native amyloid. Conversely, other did not form amyloid-like under conditions. findings suggest sequence 106-147 formation related