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

Fabrizio Tagliavini, Frances Prelli, Laura Verga, Giorgio Giaccone, Ragupathy Sarma, Peter Gorevic, Bernardino Ghetti, Flavio Passerini, Elena Ghibaudi, Gianluigi Forloni, Mario Salmona, Orso Bugiani, Blas Frangione

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235 Scopus citations


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

Original languageEnglish
Pages (from-to)9678-9682
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
StatePublished - 15 Oct 1993
Externally publishedYes


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