Amyloid protein of Gerstmann - Sträussler - Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58

Fabrizio Tagliavini, Frances Prelli, Jorge Ghiso, Orso Bugiani, Dan Serban, Stanley B. Prusiner, Martin Farlow, Bernardino Ghetti, Blas Frangione

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

Gerstmann-Sträussler-Scheinker (GSS) disease is a familial neurological disorder pathologically characterized by amyloid deposition in the cerebrum and cerebellum. The GSS amyloid is immunoreactive to antisera raised against the hamster prion protein (PrP) 27-30. This is a proteinase K-resistant glycoprotein of 27-30 kd that is derived from an abnormal isoform of a neuronal glycoprotein of 33-35 kd designated PrPSc and is a molecular marker of amyloid fibrils isolated from animals with scrapie and humans with related disorders. We have purified and characterized proteins extracted from amyloid plaque cores isolated from two patients of the Indiana kindred of GSS disease. We found that the major component of GSS amyloid is an 11 kd degradation product of PrP, whose N-terminus corresponds to the glycine residue at position 58 of the amino acid sequence deduced from the human PrP cDNA. In addition, amyloid fractions contained larger PrP fragments with apparently intact N-termini and amyloid P component. These findings suggest that the disease process leads to proteolytic cleavage of PrP, generating an amyloidogenic peptide that polymerizes into insoluble fibrils. The N-terminal cleavage of PrP in GSS disease occurs at a tryptophan- glycine peptide bond identical to that cleaved by proteinase K in vitro to generate PrP 27-30 from hamster PrPSc at codon 90. Since no mutations of the structural PrP gene have been found in the Indiana family of GSS disease, it is conceivable that factors other than the primary structure of PrP play a crucial role in the process of amyloid formation and the development of clinical neurologic dysfunction.

Original languageEnglish
Pages (from-to)513-519
Number of pages7
JournalEMBO Journal
Volume10
Issue number3
StatePublished - 1991

Fingerprint

Amyloidogenic Proteins
Codon
Glycine
Amyloid
Endopeptidase K
Cricetinae
Glycoproteins
Serum Amyloid P-Component
Prion Proteins
Prions
Scrapie
Peptides
Amyloid Plaques
Cerebrum
Neurologic Manifestations
Nervous System Diseases
Tryptophan
Cerebellum
Immune Sera
Amino Acid Sequence

Keywords

  • Amyloid protein
  • Biochemistry
  • Gerstmann-Sträussler-Scheinker disease
  • P component
  • Prion protein

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Tagliavini, F., Prelli, F., Ghiso, J., Bugiani, O., Serban, D., Prusiner, S. B., ... Frangione, B. (1991). Amyloid protein of Gerstmann - Sträussler - Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58. EMBO Journal, 10(3), 513-519.

Amyloid protein of Gerstmann - Sträussler - Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58. / Tagliavini, Fabrizio; Prelli, Frances; Ghiso, Jorge; Bugiani, Orso; Serban, Dan; Prusiner, Stanley B.; Farlow, Martin; Ghetti, Bernardino; Frangione, Blas.

In: EMBO Journal, Vol. 10, No. 3, 1991, p. 513-519.

Research output: Contribution to journalArticle

Tagliavini, Fabrizio ; Prelli, Frances ; Ghiso, Jorge ; Bugiani, Orso ; Serban, Dan ; Prusiner, Stanley B. ; Farlow, Martin ; Ghetti, Bernardino ; Frangione, Blas. / Amyloid protein of Gerstmann - Sträussler - Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58. In: EMBO Journal. 1991 ; Vol. 10, No. 3. pp. 513-519.
@article{1d65bdd89c1e493895e559c34b3bbf29,
title = "Amyloid protein of Gerstmann - Str{\"a}ussler - Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58",
abstract = "Gerstmann-Str{\"a}ussler-Scheinker (GSS) disease is a familial neurological disorder pathologically characterized by amyloid deposition in the cerebrum and cerebellum. The GSS amyloid is immunoreactive to antisera raised against the hamster prion protein (PrP) 27-30. This is a proteinase K-resistant glycoprotein of 27-30 kd that is derived from an abnormal isoform of a neuronal glycoprotein of 33-35 kd designated PrPSc and is a molecular marker of amyloid fibrils isolated from animals with scrapie and humans with related disorders. We have purified and characterized proteins extracted from amyloid plaque cores isolated from two patients of the Indiana kindred of GSS disease. We found that the major component of GSS amyloid is an 11 kd degradation product of PrP, whose N-terminus corresponds to the glycine residue at position 58 of the amino acid sequence deduced from the human PrP cDNA. In addition, amyloid fractions contained larger PrP fragments with apparently intact N-termini and amyloid P component. These findings suggest that the disease process leads to proteolytic cleavage of PrP, generating an amyloidogenic peptide that polymerizes into insoluble fibrils. The N-terminal cleavage of PrP in GSS disease occurs at a tryptophan- glycine peptide bond identical to that cleaved by proteinase K in vitro to generate PrP 27-30 from hamster PrPSc at codon 90. Since no mutations of the structural PrP gene have been found in the Indiana family of GSS disease, it is conceivable that factors other than the primary structure of PrP play a crucial role in the process of amyloid formation and the development of clinical neurologic dysfunction.",
keywords = "Amyloid protein, Biochemistry, Gerstmann-Str{\"a}ussler-Scheinker disease, P component, Prion protein",
author = "Fabrizio Tagliavini and Frances Prelli and Jorge Ghiso and Orso Bugiani and Dan Serban and Prusiner, {Stanley B.} and Martin Farlow and Bernardino Ghetti and Blas Frangione",
year = "1991",
language = "English",
volume = "10",
pages = "513--519",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Amyloid protein of Gerstmann - Sträussler - Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58

AU - Tagliavini, Fabrizio

AU - Prelli, Frances

AU - Ghiso, Jorge

AU - Bugiani, Orso

AU - Serban, Dan

AU - Prusiner, Stanley B.

AU - Farlow, Martin

AU - Ghetti, Bernardino

AU - Frangione, Blas

PY - 1991

Y1 - 1991

N2 - Gerstmann-Sträussler-Scheinker (GSS) disease is a familial neurological disorder pathologically characterized by amyloid deposition in the cerebrum and cerebellum. The GSS amyloid is immunoreactive to antisera raised against the hamster prion protein (PrP) 27-30. This is a proteinase K-resistant glycoprotein of 27-30 kd that is derived from an abnormal isoform of a neuronal glycoprotein of 33-35 kd designated PrPSc and is a molecular marker of amyloid fibrils isolated from animals with scrapie and humans with related disorders. We have purified and characterized proteins extracted from amyloid plaque cores isolated from two patients of the Indiana kindred of GSS disease. We found that the major component of GSS amyloid is an 11 kd degradation product of PrP, whose N-terminus corresponds to the glycine residue at position 58 of the amino acid sequence deduced from the human PrP cDNA. In addition, amyloid fractions contained larger PrP fragments with apparently intact N-termini and amyloid P component. These findings suggest that the disease process leads to proteolytic cleavage of PrP, generating an amyloidogenic peptide that polymerizes into insoluble fibrils. The N-terminal cleavage of PrP in GSS disease occurs at a tryptophan- glycine peptide bond identical to that cleaved by proteinase K in vitro to generate PrP 27-30 from hamster PrPSc at codon 90. Since no mutations of the structural PrP gene have been found in the Indiana family of GSS disease, it is conceivable that factors other than the primary structure of PrP play a crucial role in the process of amyloid formation and the development of clinical neurologic dysfunction.

AB - Gerstmann-Sträussler-Scheinker (GSS) disease is a familial neurological disorder pathologically characterized by amyloid deposition in the cerebrum and cerebellum. The GSS amyloid is immunoreactive to antisera raised against the hamster prion protein (PrP) 27-30. This is a proteinase K-resistant glycoprotein of 27-30 kd that is derived from an abnormal isoform of a neuronal glycoprotein of 33-35 kd designated PrPSc and is a molecular marker of amyloid fibrils isolated from animals with scrapie and humans with related disorders. We have purified and characterized proteins extracted from amyloid plaque cores isolated from two patients of the Indiana kindred of GSS disease. We found that the major component of GSS amyloid is an 11 kd degradation product of PrP, whose N-terminus corresponds to the glycine residue at position 58 of the amino acid sequence deduced from the human PrP cDNA. In addition, amyloid fractions contained larger PrP fragments with apparently intact N-termini and amyloid P component. These findings suggest that the disease process leads to proteolytic cleavage of PrP, generating an amyloidogenic peptide that polymerizes into insoluble fibrils. The N-terminal cleavage of PrP in GSS disease occurs at a tryptophan- glycine peptide bond identical to that cleaved by proteinase K in vitro to generate PrP 27-30 from hamster PrPSc at codon 90. Since no mutations of the structural PrP gene have been found in the Indiana family of GSS disease, it is conceivable that factors other than the primary structure of PrP play a crucial role in the process of amyloid formation and the development of clinical neurologic dysfunction.

KW - Amyloid protein

KW - Biochemistry

KW - Gerstmann-Sträussler-Scheinker disease

KW - P component

KW - Prion protein

UR - http://www.scopus.com/inward/record.url?scp=0026033998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026033998&partnerID=8YFLogxK

M3 - Article

C2 - 1672107

AN - SCOPUS:0026033998

VL - 10

SP - 513

EP - 519

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 3

ER -