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 language | English |
|---|---|
| Pages (from-to) | 695-703 |
| Number of pages | 9 |
| Journal | Cell |
| Volume | 79 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Nov 18 1994 |
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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 R.; Dlouhy, Stephen R.; Ghetti, Bernardino; Bugiani, Orso; Frangione, Blas.
In: Cell, Vol. 79, No. 4, 18.11.1994, p. 695-703.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Amyloid fibrils in Gerstmann-Sträussler-Scheinker disease (Indiana and Swedish Kindreds) express only PrP peptides encoded by the mutant allele
AU - Tagliavini, Fabrizio
AU - Prelli, Frances
AU - Porro, Monica
AU - Rossi, Giacomina
AU - Giaccone, Giorgio
AU - Farlow, Martin R.
AU - Dlouhy, Stephen R.
AU - Ghetti, Bernardino
AU - Bugiani, Orso
AU - Frangione, Blas
PY - 1994/11/18
Y1 - 1994/11/18
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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UR - http://www.scopus.com/inward/citedby.url?scp=0028004290&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(94)90554-1
DO - 10.1016/0092-8674(94)90554-1
M3 - Article
C2 - 7954833
AN - SCOPUS:0028004290
VL - 79
SP - 695
EP - 703
JO - Cell
JF - Cell
SN - 0092-8674
IS - 4
ER -