Amyloid fibrils in Gerstmann-Sträussler-Scheinker disease (Indiana and Swedish Kindreds) express only PrP peptides encoded by the mutant allele

Fabrizio Tagliavini, Frances Prelli, Monica Porro, Giacomina Rossi, Giorgio Giaccone, Martin Farlow, Stephen Dlouhy, Bernardino Ghetti, Orso Bugiani, Blas Frangione

Research output: Contribution to journalArticle

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Abstract

Gerstmann-Sträussler-Scheinker (GSS) disease is a cerebral amyloidosis linked to mutations of the PRNP gene. We previously reported that the amyloid protein in the Indiana kindred of GSS is an internal fragment of prion protein (PrP). To investigate whether this fragment originates only from mutant or from both mutant and wild-type PrP, we have characterized amyloid proteins purified from patients of the Indiana and Swedish GSS families. These patients were heterozygous for the Met-Val polymorphism at PRNP codon 129 and carried a mutation at PRNP codon 198 (Phe→Ser) and codon 217 (Gln→Arg), respectively. The smallest amyloid subunit was a 7 kDa peptide spanning residues ∼81 to ∼150 in the Indiana patient and ∼81 to ∼146 in the Swedish patient. In both patients, only Val was present at position 129. Since Val-129 was in coupling phase with Ser-198 and Arg-217, our findings indicate that only the mutant PrP is involved in amyloid formation in both kindreds.

Original languageEnglish
Pages (from-to)695-703
Number of pages9
JournalCell
Volume79
Issue number4
DOIs
StatePublished - Nov 18 1994

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Amyloid
Amyloidogenic Proteins
Alleles
Peptides
Codon
Polymorphism
Genes
Mutation
Mutant Proteins
Prion Proteins
Prions

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Amyloid fibrils in Gerstmann-Sträussler-Scheinker disease (Indiana and Swedish Kindreds) express only PrP peptides encoded by the mutant allele. / Tagliavini, Fabrizio; Prelli, Frances; Porro, Monica; Rossi, Giacomina; Giaccone, Giorgio; Farlow, Martin; Dlouhy, Stephen; Ghetti, Bernardino; Bugiani, Orso; Frangione, Blas.

In: Cell, Vol. 79, No. 4, 18.11.1994, p. 695-703.

Research output: Contribution to journalArticle

Tagliavini, Fabrizio ; Prelli, Frances ; Porro, Monica ; Rossi, Giacomina ; Giaccone, Giorgio ; Farlow, Martin ; Dlouhy, Stephen ; Ghetti, Bernardino ; Bugiani, Orso ; Frangione, Blas. / Amyloid fibrils in Gerstmann-Sträussler-Scheinker disease (Indiana and Swedish Kindreds) express only PrP peptides encoded by the mutant allele. In: Cell. 1994 ; Vol. 79, No. 4. pp. 695-703.
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abstract = "Gerstmann-Str{\"a}ussler-Scheinker (GSS) disease is a cerebral amyloidosis linked to mutations of the PRNP gene. We previously reported that the amyloid protein in the Indiana kindred of GSS is an internal fragment of prion protein (PrP). To investigate whether this fragment originates only from mutant or from both mutant and wild-type PrP, we have characterized amyloid proteins purified from patients of the Indiana and Swedish GSS families. These patients were heterozygous for the Met-Val polymorphism at PRNP codon 129 and carried a mutation at PRNP codon 198 (Phe→Ser) and codon 217 (Gln→Arg), respectively. The smallest amyloid subunit was a 7 kDa peptide spanning residues ∼81 to ∼150 in the Indiana patient and ∼81 to ∼146 in the Swedish patient. In both patients, only Val was present at position 129. Since Val-129 was in coupling phase with Ser-198 and Arg-217, our findings indicate that only the mutant PrP is involved in amyloid formation in both kindreds.",
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AU - Tagliavini, Fabrizio

AU - Prelli, Frances

AU - Porro, Monica

AU - Rossi, Giacomina

AU - Giaccone, Giorgio

AU - Farlow, Martin

AU - Dlouhy, Stephen

AU - Ghetti, Bernardino

AU - Bugiani, Orso

AU - Frangione, Blas

PY - 1994/11/18

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N2 - Gerstmann-Sträussler-Scheinker (GSS) disease is a cerebral amyloidosis linked to mutations of the PRNP gene. We previously reported that the amyloid protein in the Indiana kindred of GSS is an internal fragment of prion protein (PrP). To investigate whether this fragment originates only from mutant or from both mutant and wild-type PrP, we have characterized amyloid proteins purified from patients of the Indiana and Swedish GSS families. These patients were heterozygous for the Met-Val polymorphism at PRNP codon 129 and carried a mutation at PRNP codon 198 (Phe→Ser) and codon 217 (Gln→Arg), respectively. The smallest amyloid subunit was a 7 kDa peptide spanning residues ∼81 to ∼150 in the Indiana patient and ∼81 to ∼146 in the Swedish patient. In both patients, only Val was present at position 129. Since Val-129 was in coupling phase with Ser-198 and Arg-217, our findings indicate that only the mutant PrP is involved in amyloid formation in both kindreds.

AB - Gerstmann-Sträussler-Scheinker (GSS) disease is a cerebral amyloidosis linked to mutations of the PRNP gene. We previously reported that the amyloid protein in the Indiana kindred of GSS is an internal fragment of prion protein (PrP). To investigate whether this fragment originates only from mutant or from both mutant and wild-type PrP, we have characterized amyloid proteins purified from patients of the Indiana and Swedish GSS families. These patients were heterozygous for the Met-Val polymorphism at PRNP codon 129 and carried a mutation at PRNP codon 198 (Phe→Ser) and codon 217 (Gln→Arg), respectively. The smallest amyloid subunit was a 7 kDa peptide spanning residues ∼81 to ∼150 in the Indiana patient and ∼81 to ∼146 in the Swedish patient. In both patients, only Val was present at position 129. Since Val-129 was in coupling phase with Ser-198 and Arg-217, our findings indicate that only the mutant PrP is involved in amyloid formation in both kindreds.

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