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Proc Natl Acad Sci U S A. 1993 Oct 15; 90(20): 9678–9682.

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


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 approximately 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.

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  • Oesch B, Westaway D, Wälchli M, McKinley MP, Kent SB, Aebersold R, Barry RA, Tempst P, Teplow DB, Hood LE, et al. A cellular gene encodes scrapie PrP 27-30 protein. Cell. 1985 Apr;40(4):735–746. [PubMed]
  • Chesebro B, Race R, Wehrly K, Nishio J, Bloom M, Lechner D, Bergstrom S, Robbins K, Mayer L, Keith JM, et al. Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. Nature. 1985 May 23;315(6017):331–333. [PubMed]
  • Kretzschmar HA, Prusiner SB, Stowring LE, DeArmond SJ. Scrapie prion proteins are synthesized in neurons. Am J Pathol. 1986 Jan;122(1):1–5. [PMC free article] [PubMed]
  • Stahl N, Borchelt DR, Hsiao K, Prusiner SB. Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell. 1987 Oct 23;51(2):229–240. [PubMed]
  • Tagliavini F, Prelli F, Porro M, Salmona M, Bugiani O, Frangione B. A soluble form of prion protein in human cerebrospinal fluid: implications for prion-related encephalopathies. Biochem Biophys Res Commun. 1992 May 15;184(3):1398–1404. [PubMed]
  • Prusiner SB. Chemistry and biology of prions. Biochemistry. 1992 Dec 15;31(49):12277–12288. [PubMed]
  • Bolton DC, McKinley MP, Prusiner SB. Identification of a protein that purifies with the scrapie prion. Science. 1982 Dec 24;218(4579):1309–1311. [PubMed]
  • Prusiner SB, Bolton DC, Groth DF, Bowman KA, Cochran SP, McKinley MP. Further purification and characterization of scrapie prions. Biochemistry. 1982 Dec 21;21(26):6942–6950. [PubMed]
  • McKinley MP, Bolton DC, Prusiner SB. A protease-resistant protein is a structural component of the scrapie prion. Cell. 1983 Nov;35(1):57–62. [PubMed]
  • Prusiner SB, Groth DF, Bolton DC, Kent SB, Hood LE. Purification and structural studies of a major scrapie prion protein. Cell. 1984 Aug;38(1):127–134. [PubMed]
  • Prusiner SB, McKinley MP, Bowman KA, Bolton DC, Bendheim PE, Groth DF, Glenner GG. Scrapie prions aggregate to form amyloid-like birefringent rods. Cell. 1983 Dec;35(2 Pt 1):349–358. [PubMed]
  • Gasset M, Baldwin MA, Fletterick RJ, Prusiner SB. Perturbation of the secondary structure of the scrapie prion protein under conditions that alter infectivity. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):1–5. [PMC free article] [PubMed]
  • Hsiao K, Dlouhy SR, Farlow MR, Cass C, Da Costa M, Conneally PM, Hodes ME, Ghetti B, Prusiner SB. Mutant prion proteins in Gerstmann-Sträussler-Scheinker disease with neurofibrillary tangles. Nat Genet. 1992 Apr;1(1):68–71. [PubMed]
  • Dlouhy SR, Hsiao K, Farlow MR, Foroud T, Conneally PM, Johnson P, Prusiner SB, Hodes ME, Ghetti B. Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene. Nat Genet. 1992 Apr;1(1):64–67. [PubMed]
  • Ghetti B, Tagliavini F, Masters CL, Beyreuther K, Giaccone G, Verga L, Farlow MR, Conneally PM, Dlouhy SR, Azzarelli B, et al. Gerstmann-Sträussler-Scheinker disease. II. Neurofibrillary tangles and plaques with PrP-amyloid coexist in an affected family. Neurology. 1989 Nov;39(11):1453–1461. [PubMed]
  • Giaccone G, Tagliavini F, Verga L, Frangione B, Farlow MR, Bugiani O, Ghetti B. Neurofibrillary tangles of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease share antigenic determinants with those of Alzheimer disease. Brain Res. 1990 Oct 22;530(2):325–329. [PubMed]
  • Tagliavini F, Giaccone G, Prelli F, Verga L, Porro M, Trojanowski JQ, Farlow MR, Frangione B, Ghetti B, Bugiani O. A68 is a component of paired helical filaments of Gerstmann-Sträussler-Scheinker disease, Indiana kindred. Brain Res. 1993 Jul 9;616(1-2):325–329. [PubMed]
  • Tagliavini F, Prelli F, Ghiso J, Bugiani O, Serban D, Prusiner SB, Farlow MR, Ghetti B, Frangione B. 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 J. 1991 Mar;10(3):513–519. [PMC free article] [PubMed]
  • Giaccone G, Verga L, Bugiani O, Frangione B, Serban D, Prusiner SB, Farlow MR, Ghetti B, Tagliavini F. Prion protein preamyloid and amyloid deposits in Gerstmann-Sträussler-Scheinker disease, Indiana kindred. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9349–9353. [PMC free article] [PubMed]
  • Garnier J, Osguthorpe DJ, Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. [PubMed]
  • Eisenberg D, Schwarz E, Komaromy M, Wall R. Analysis of membrane and surface protein sequences with the hydrophobic moment plot. J Mol Biol. 1984 Oct 15;179(1):125–142. [PubMed]
  • Chou PY, Fasman GD. Empirical predictions of protein conformation. Annu Rev Biochem. 1978;47:251–276. [PubMed]
  • Gorevic PD, Castano EM, Sarma R, Frangione B. Ten to fourteen residue peptides of Alzheimer's disease protein are sufficient for amyloid fibril formation and its characteristic x-ray diffraction pattern. Biochem Biophys Res Commun. 1987 Sep 15;147(2):854–862. [PubMed]
  • Gasset M, Baldwin MA, Lloyd DH, Gabriel JM, Holtzman DM, Cohen F, Fletterick R, Prusiner SB. Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10940–10944. [PMC free article] [PubMed]
  • Doh-ura K, Tateishi J, Sasaki H, Kitamoto T, Sakaki Y. Pro----leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Sträussler syndrome. Biochem Biophys Res Commun. 1989 Sep 15;163(2):974–979. [PubMed]
  • Goldfarb LG, Petersen RB, Tabaton M, Brown P, LeBlanc AC, Montagna P, Cortelli P, Julien J, Vital C, Pendelbury WW, et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. Science. 1992 Oct 30;258(5083):806–808. [PubMed]
  • Castaño EM, Wisniewski T, Frangione B. Inherited amyloids of the nervous system. Curr Opin Neurobiol. 1991 Oct;1(3):448–454. [PubMed]
  • Goldfarb LG, Brown P, Haltia M, Ghiso J, Frangione B, Gajdusek DC. Synthetic peptides corresponding to different mutated regions of the amyloid gene in familial Creutzfeldt-Jakob disease show enhanced in vitro formation of morphologically different amyloid fibrils. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4451–4454. [PMC free article] [PubMed]
  • Levy E, Carman MD, Fernandez-Madrid IJ, Power MD, Lieberburg I, van Duinen SG, Bots GT, Luyendijk W, Frangione B. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science. 1990 Jun 1;248(4959):1124–1126. [PubMed]
  • Prelli F, Levy E, van Duinen SG, Bots GT, Luyendijk W, Frangione B. Expression of a normal and variant Alzheimer's beta-protein gene in amyloid of hereditary cerebral hemorrhage, Dutch type: DNA and protein diagnostic assays. Biochem Biophys Res Commun. 1990 Jul 16;170(1):301–307. [PubMed]
  • Levy E, Haltia M, Fernandez-Madrid I, Koivunen O, Ghiso J, Prelli F, Frangione B. Mutation in gelsolin gene in Finnish hereditary amyloidosis. J Exp Med. 1990 Dec 1;172(6):1865–1867. [PMC free article] [PubMed]
  • Maury CP. Gelsolin-related amyloidosis. Identification of the amyloid protein in Finnish hereditary amyloidosis as a fragment of variant gelsolin. J Clin Invest. 1991 Apr;87(4):1195–1199. [PMC free article] [PubMed]
  • Wisniewski T, Ghiso J, Frangione B. Peptides homologous to the amyloid protein of Alzheimer's disease containing a glutamine for glutamic acid substitution have accelerated amyloid fibril formation. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1247–1254. [PubMed]
  • Maury CP, Nurmiaho-Lassila EL. Creation of amyloid fibrils from mutant Asn187 gelsolin peptides. Biochem Biophys Res Commun. 1992 Feb 28;183(1):227–231. [PubMed]
  • Fraser PE, Nguyen JT, Inouye H, Surewicz WK, Selkoe DJ, Podlisny MB, Kirschner DA. Fibril formation by primate, rodent, and Dutch-hemorrhagic analogues of Alzheimer amyloid beta-protein. Biochemistry. 1992 Nov 10;31(44):10716–10723. [PubMed]
  • Diringer H, Gelderblom H, Hilmert H, Ozel M, Edelbluth C, Kimberlin RH. Scrapie infectivity, fibrils and low molecular weight protein. Nature. 1983 Dec 1;306(5942):476–478. [PubMed]
  • Merz PA, Rohwer RG, Kascsak R, Wisniewski HM, Somerville RA, Gibbs CJ, Jr, Gajdusek DC. Infection-specific particle from the unconventional slow virus diseases. Science. 1984 Jul 27;225(4660):437–440. [PubMed]
  • Glenner GG, Eanes ED, Bladen HA, Linke RP, Termine JD. Beta-pleated sheet fibrils. A comparison of native amyloid with synthetic protein fibrils. J Histochem Cytochem. 1974 Dec;22(12):1141–1158. [PubMed]
  • Kirschner DA, Abraham C, Selkoe DJ. X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-beta conformation. Proc Natl Acad Sci U S A. 1986 Jan;83(2):503–507. [PMC free article] [PubMed]
  • Kirschner DA, Inouye H, Duffy LK, Sinclair A, Lind M, Selkoe DJ. Synthetic peptide homologous to beta protein from Alzheimer disease forms amyloid-like fibrils in vitro. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6953–6957. [PMC free article] [PubMed]
  • Fraser PE, Nguyen JT, Surewicz WK, Kirschner DA. pH-dependent structural transitions of Alzheimer amyloid peptides. Biophys J. 1991 Nov;60(5):1190–1201. [PMC free article] [PubMed]
  • Glenner GG, Eanes ED, Wiley CA. Amyloid fibrils formed from a segment of the pancreatic islet amyloid protein. Biochem Biophys Res Commun. 1988 Sep 15;155(2):608–614. [PubMed]
  • Forloni G, Angeretti N, Chiesa R, Monzani E, Salmona M, Bugiani O, Tagliavini F. Neurotoxicity of a prion protein fragment. Nature. 1993 Apr 8;362(6420):543–546. [PubMed]

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