Skip to main content
SpringerLink
Log in
Book cover

Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases pp 289–317Cite as

Structural Studies of Prion Proteins and Prions

  • Chapter
  • First Online:

Abstract

Prion diseases are a group of fatal and incurable neurodegenerative ­disorders of mammals. They uniquely manifest as sporadic, genetic, and infectious maladies. The agent responsible for prion diseases is the prion. A prion is defined as a proteinaceous infectious particle, which is solely constituted by an alternately folded form of the prion protein (PrP) (Prusiner 1982).

In diseased animals and humans, PrP exists in two forms, the physiological, cellular form of PrP, PrPC, and the pathological prion form denoted as PrPSc. The mechanism whereby nascent PrPSc is generated is currently unknown. Structural studies of either isoform are of great importance for understanding the biology of prion diseases since they may clarify the molecular mechanisms responsible for these pathologies. In this chapter, we present an overview of the studies into PrPC as well as structures of prions.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Adrover M, Pauwels K, Pringent S, De Chiara C, Xu Z, Chapuis C, Pastore A, Rezaei H (2010) Prion fibrillization is mediated by a native structural element which comprises the helices H2 and H3. J Biol Chem 285:21004–21012

    PubMed  CAS  Google Scholar 

  • Aguzzi A, Sigurdson C, Heikenwaelder M (2008) Molecular mechanisms of prion pathogenesis. Annu Rev Pathol 3:11–40

    PubMed  CAS  Google Scholar 

  • Alper T, Cramp WA, Haig DA, Clarke MC (1967) Does the agent of scrapie replicate without nucleic acid? Nature 214:764–766

    PubMed  CAS  Google Scholar 

  • Anderson M, Bocharova OV, Makarava N, Breydo L, Salnikov VV, Baskakov IV (2006) Polymorphism and ultrastructural organization of prion protein amyloid fibrils: An insight from high resolution atomic force microscopy. J Mol Biol 358:580–596

    PubMed  CAS  Google Scholar 

  • Antonyuk SV, Trevitt CR, Strange RW, Jackson GS, Sangar D, Batchelor M, Cooper S, Fraser C, Jones S, Georgiou T, Khalili-Shirazi A, Clarke AR, Hasnain SS, Collinge J (2009) Crystal structure of human prion protein bound to a therapeutic antibody. Proc Natl Acad Sci USA 106:2554–2558

    PubMed  CAS  Google Scholar 

  • Apetri AC, Surewicz K, Surewicz WK (2004) The effect of disease-associated mutations on the folding pathway of human prion protein. J Biol Chem 279:18008–18014

    PubMed  CAS  Google Scholar 

  • Ashok A, Hegde RS (2009) Selective processing and metabolism of disease-causing mutant prion proteins. PLoS Pathog 5:e1000479

    PubMed  Google Scholar 

  • Bae SH, Legname G, Serban A, Prusiner SB, Wright PE, Dyson HJ (2009) Prion proteins with ­pathogenic and protective mutations show similar structure and dynamics. Biochemistry 48:8120–8128

    PubMed  CAS  Google Scholar 

  • Baker HE, Poulter M, Crow TJ, Frith CD, Lofthouse R, Ridley RM (1991) Aminoacid polymorphism in human prion protein and age at death in inherited prion disease. Lancet 337:1286

    PubMed  CAS  Google Scholar 

  • Balguerie A, Dos Reis S, Ritter C, Chaignepain S, Coulary-Salin B, Forge V, Bathany K, Lascu I, Schmitter JM, Riek R, Saupe SJ (2003) Domain organization and structure–function ­relationship of the HET-s prion protein of Podospora anserina. EMBO J 22:2071–2081

    PubMed  CAS  Google Scholar 

  • Bellinger-Kawahara C, Diener TO, Mckinley MP, Groth DF, Smith DR, Prusiner SB (1987) Purified scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic acids. Virology 160:271–274

    PubMed  CAS  Google Scholar 

  • Benetti F, Amenitsch H, Vos M, Peters P, Legname G, Requena JR (2010) SAXS study of Syrian hamster prion fibrils and recombinant truncated prion protein in the presence of transition ­metals (in press). In: Sartori BRM, Amenitsch H, Bernstorff S (ed) Annual report of the Austrian SAXS beamline 2009. Institute of Biophysics and Nanosystems Research, Graz

    Google Scholar 

  • Bertho G, Bouvier G, Hui Bon Hoa G, Girault JP (2008) The key-role of tyrosine 155 in the mechanism of prion transconformation as highlighted by a study of sheep mutant peptides. Peptides 29:1073–1084

    Google Scholar 

  • Bessen RA, Marsh RF (1992) Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent. J Virol 66:2096–2101

    PubMed  CAS  Google Scholar 

  • Bessen RA, Marsh RF (1994) Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. J Virol 68:7859–7868

    PubMed  CAS  Google Scholar 

  • Bignami A, Parry HB (1971) Aggregations of 35-nanometer particles associated with neuronal cytopathic changes in natural scrapie. Science 171:389–399

    PubMed  CAS  Google Scholar 

  • Biverstahl H, Andersson A, Graslund A, Maler L (2004) NMR solution structure and membrane interaction of the N-terminal sequence (1–30) of the bovine prion protein. Biochemistry 43:14940–14947

    PubMed  Google Scholar 

  • Borchelt DR, Taraboulos A, Prusiner SB (1992) Evidence for synthesis of scrapie prion proteins in the endocytic pathway. J Biol Chem 267:16188–16199

    PubMed  CAS  Google Scholar 

  • Bots GT, De Man JC, Verjaal A (1971) Virus-like particles in brain tissue from two patients with Creutzfeldt–Jakob disease. Acta Neuropathol 18:267–270

    PubMed  CAS  Google Scholar 

  • Bueler H, Aguzzi A, Sailer A, Greiner RA, Autenried P, Aguet M, Weissmann C (1993) Mice devoid of PrP are resistant to scrapie. Cell 73:1339–1347

    PubMed  CAS  Google Scholar 

  • Burns CS, Aronoff-Spencer E, Legname G, Prusiner SB, Antholine WE, Gerfen GJ, Peisach J, Millhauser GL (2003) Copper coordination in the full-length, recombinant prion protein. Biochemistry 42:6794–6803

    PubMed  CAS  Google Scholar 

  • Calzolai L, Zahn R (2003) Influence of pH on NMR structure and stability of the human prion protein globular domain. J Biol Chem 278:35592–35596

    PubMed  CAS  Google Scholar 

  • Calzolai L, Lysek DA, Guntert P, Von Schroetter C, Riek R, Zahn R, Wuthrich K (2000) NMR structures of three single-residue variants of the human prion protein. Proc Natl Acad Sci USA 97:8340–8345

    PubMed  CAS  Google Scholar 

  • Calzolai L, Lysek DA, Perez DR, Guntert P, Wuthrich K (2005) Prion protein NMR structures of chickens, turtles, and frogs. Proc Natl Acad Sci USA 102:651–655

    PubMed  CAS  Google Scholar 

  • Campana V, Sarnataro D, Zurzolo C (2005) The highways and byways of prion protein trafficking. Trends Cell Biol 15:102–111

    PubMed  CAS  Google Scholar 

  • Caughey B (1991) Cellular metabolism of PrP. Prion Diseases in Humans and Animals Conference, London

    Google Scholar 

  • Caughey BW, Dong A, Bhat KS, Ernst D, Hayes SF, Caughey WS (1991) Secondary structure analysis of the scrapie-associated protein PrP 27–30 in water by infrared spectroscopy. Biochemistry 30:7672–7680

    PubMed  CAS  Google Scholar 

  • Caughey B, Raymond GJ, Bessen RA (1998) Strain-dependent differences in β-sheet conformations of abnormal prion protein. J Biol Chem 273:32230–32235

    PubMed  CAS  Google Scholar 

  • Chesebro B (1992) PrP and the scrapie agent. Nature 356:560

    PubMed  CAS  Google Scholar 

  • Chesebro B, Trifilo M, Race R, Meade-White K, Teng C, Lacasse R, Raymond L, Favara C, Baron G, Priola S, Caughey B, Masliah E, Oldstone M (2005) Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308:1435–1439

    PubMed  CAS  Google Scholar 

  • Chiesa R, Piccardo P, Ghetti B, Harris DA (1998) Neurological illness in transgenic mice ­expressing a prion protein with an insertional mutation. Neuron 21:1339–1351

    PubMed  CAS  Google Scholar 

  • Christen B, Perez DR, Hornemann S, Wuthrich K (2008) NMR structure of the bank vole prion protein at 20 °C contains a structured loop of residues 165–171. J Mol Biol 383:306–312

    PubMed  CAS  Google Scholar 

  • Christen B, Hornemann S, Damberger FF, Wuthrich K (2009) Prion protein NMR structure from Tammar Wallaby (Macropus eugenii) shows that the β2–α2 loop is modulated by long-range sequence effects. J Mol Biol 389:833–845

    PubMed  CAS  Google Scholar 

  • Cohen FE, Prusiner SB (1998) Pathologic conformations of prion proteins. Annu Rev Biochem 67:793–819

    PubMed  CAS  Google Scholar 

  • Collinge J (2001) Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 24:519–550

    PubMed  CAS  Google Scholar 

  • Collinge J, Palmer MS, Dryden AJ (1991) Genetic predisposition to iatrogenic Creutzfeldt–Jakob disease. Lancet 337:1441–1442

    PubMed  CAS  Google Scholar 

  • David-Ferreira JF, David-Ferreira KL, Gibbs CJ Jr, Morris JA (1968) Scrapie in mice: Ultrastructural observations in the cerebral cortex. Proc Soc Exp Biol Med 127:313–320

    PubMed  CAS  Google Scholar 

  • Demarco ML, Daggett V (2004) From conversion to aggregation: protofibril formation of the prion protein. Proc Natl Acad Sci USA 101:2293–2298

    PubMed  CAS  Google Scholar 

  • Demarco ML, Silveira J, Caughey B, Daggett V (2006) Structural properties of prion protein protofibrils and fibrils: an experimental assessment of atomic models. Biochemistry 45:15573–15582

    PubMed  CAS  Google Scholar 

  • Diener TO, Mckinley MP, Prusiner SB (1982) Viroids and prions. Proc Natl Acad Sci USA 79:5220–5224

    PubMed  CAS  Google Scholar 

  • Donne DG, Viles JH, Groth D, Mehlhorn I, James TL, Cohen FE, Prusiner SB, Wright PE, Dyson HJ (1997) Structure of the recombinant full-length hamster prion protein PrP(29–231): the N-terminus is highly flexible. Proc Natl Acad Sci USA 94:13452–13457

    PubMed  CAS  Google Scholar 

  • Dossena S, Imeri L, Mangieri M, Garofoli A, Ferrari L, Senatore A, Restelli E, Balducci C, Fiordaliso F, Salio M, Bianchi S, Fioriti L, Morbin M, Pincherle A, Marcon G, Villani F, Carli M, Tagliavini F, Forloni G, Chiesa R (2008) Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model. Neuron 60:598–609

    PubMed  CAS  Google Scholar 

  • Eghiaian F, Grosclaude J, Lesceu S, Debey P, Doublet B, Treguer E, Rezaei H, Knossow M (2004) Insight into the PrPC  →  PrPSc conversion from the structures of antibody-bound ovine prion scrapie-susceptibility variants. Proc Natl Acad Sci USA 101:10254–10259

    PubMed  CAS  Google Scholar 

  • Fischer M, Rulicke T, Raeber A, Sailer A, Moser M, Oesch B, Brandner S, Aguzzi A, Weissmann C (1996) Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO J 15:1255–1264

    PubMed  CAS  Google Scholar 

  • Gasset M, Baldwin MA, Fletterick RJ, Prusiner SB (1993) Perturbation of the secondary structure of the scrapie prion protein under conditions that alter infectivity. Proc Natl Acad Sci USA 90:1–5

    PubMed  CAS  Google Scholar 

  • Godsave SF, Wille H, Kujala P, Latawiec D, Dearmond SJ, Serban A, Prusiner SB, Peters PJ (2008) Cryo-immunogold electron microscopy for prions: toward identification of a conversion site. J Neurosci 28:12489–12499

    PubMed  CAS  Google Scholar 

  • Goormaghtigh E, Cabiaux V, Ruysschaert J-M (1990) Secondary structure and dosage of soluble membrane proteins by attenuated total reflection Fourier-transform infrared spectroscopy on hydrated films. Eur J Biochem 193:409–420

    PubMed  CAS  Google Scholar 

  • Gorodinsky A, Harris DA (1995) Glycolipid-anchored proteins in neuroblastoma cells form detergent-resistant complexes without caveolin. J Cell Biol 129:619–627

    PubMed  CAS  Google Scholar 

  • Gossert AD, Bonjour S, Lysek DA, Fiorito F, Wuthrich K (2005) Prion protein NMR structures of elk and of mouse/elk hybrids. Proc Natl Acad Sci USA 102:646–650

    PubMed  CAS  Google Scholar 

  • Govaerts C, Wille H, Prusiner SB, Cohen FE (2004) Evidence for assembly of prions with left-handed β-helices into trimers. Proc Natl Acad Sci USA 101:8342–8347

    PubMed  CAS  Google Scholar 

  • Haire LF, Whyte SM, Vasisht N, Gill AC, Verma C, Dodson EJ, Dodson GG, Bayley PM (2004) The crystal structure of the globular domain of sheep prion protein. J Mol Biol 336:1175–1183

    PubMed  CAS  Google Scholar 

  • Hegde RS, Mastrianni JA, Scott MR, Defea KA, Tremblay P, Torchia M, Dearmond SJ, Prusiner SB, Lingappa VR (1998) A transmembrane form of the prion protein in neurodegenerative disease. Science 279:827–834

    PubMed  CAS  Google Scholar 

  • Hegde RS, Tremblay P, Groth D, Dearmond SJ, Prusiner SB, Lingappa VR (1999) Transmissible and genetic prion diseases share a common pathway of neurodegeneration. Nature 402:822–826

    PubMed  CAS  Google Scholar 

  • Heske J, Heller U, Winklhofer KF, Tatzelt J (2004) The C-terminal globular domain of the prion protein is necessary and sufficient for import into the endoplasmic reticulum. J Biol Chem 279:5435–5443

    PubMed  CAS  Google Scholar 

  • Hill AF, Antoniou M, Collinge J (1999) Protease-resistant prion protein produced in vitro lacks detectable infectivity. J Gen Virol 80(Pt 1):11–14

    PubMed  CAS  Google Scholar 

  • Hornemann S, Von Schroetter C, Damberger FF, Wuthrich K (2009) Prion protein-detergent micelle interactions studied by NMR in solution. J Biol Chem 284:22713–22721

    PubMed  CAS  Google Scholar 

  • Hsiao KK, Scott M, Foster D, Groth DF, Dearmond SJ, Prusiner SB (1990) Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science 250:1587–1590

    PubMed  CAS  Google Scholar 

  • Hsiao K, Dlouhy SR, Farlow MR, Cass C, Da Costa M, Conneally PM, Hodes ME, Ghetti B, Prusiner SB (1992) Mutant prion proteins in Gerstmann–Straüssler–Scheinker disease with neurofibrillary tangles. Nat Genet 1:68–71

    PubMed  CAS  Google Scholar 

  • Hsiao KK, Groth D, Scott M, Yang SL, Serban H, Rapp D, Foster D, Torchia M, Dearmond SJ, Prusiner SB (1994) Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein. Proc Natl Acad Sci USA 91:9126–9130

    PubMed  CAS  Google Scholar 

  • Huang Z, Prusiner SB, Cohen FE (1995) Scrapie prions: a three-dimensional model of an infectious fragment. Fold Des 1:13–19

    PubMed  Google Scholar 

  • Ilc G, Giachin G, Jaremko M, Jaremko L, Benetti F, Plavec J, Zhukov I, Legname G (2010) NMR structure of the human prion protein with the pathological Q212P mutation reveals unique structural features. PLoS One 5:e11715

    PubMed  Google Scholar 

  • James TL, Liu H, Ulyanov NB, Farr-Jones S, Zhang H, Donne DG, Kaneko K, Groth D, Mehlhorn I, Prusiner SB, Cohen FE (1997) Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform. Proc Natl Acad Sci USA 94:10086–10091

    PubMed  CAS  Google Scholar 

  • Kaneko K, Vey M, Scott M, Pilkuhn S, Cohen FE, Prusiner SB (1997a) COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into the scrapie isoform. Proc Natl Acad Sci USA 94:2333–2338

    PubMed  CAS  Google Scholar 

  • Kaneko K, Zulianello L, Scott M, Cooper CM, Wallace AC, James TL, Cohen FE, Prusiner SB (1997b) Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion propagation. Proc Natl Acad Sci USA 94:10069–10074

    PubMed  CAS  Google Scholar 

  • Kimberlin RH (1990) Scrapie and possible relationships with viroids. Semin Virol 1:153–162

    Google Scholar 

  • Knaus KJ, Morillas M, Swietnicki W, Malone M, Surewicz WK, Yee VC (2001) Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat Struct Biol 8:770–774

    PubMed  CAS  Google Scholar 

  • Kobayashi A, Hizume M, Teruya K, Mohri S, Kitamoto T (2009) Heterozygous inhibition in prion infection: the stone fence model. Prion 3:27–30

    PubMed  CAS  Google Scholar 

  • Kovacs GG, Trabattoni G, Hainfellner JA, Ironside JW, Knight RS, Budka H (2002) Mutations of the prion protein gene phenotypic spectrum. J Neurol 249:1567–1582

    PubMed  CAS  Google Scholar 

  • Kozin SA, Bertho G, Mazur AK, Rabesona H, Girault JP, Haertle T, Takahashi M, Debey P, Hoa GH (2001) Sheep prion protein synthetic peptide spanning helix 1 and β-strand 2 (residues 142–166) shows β-hairpin structure in solution. J Biol Chem 276:46364–46370

    PubMed  CAS  Google Scholar 

  • Kozin SA, Lepage C, Hui Bon Hoa G, Rabesona H, Mazur AK, Blond A, Cheminant M, Haertle T, Debey P, Rebuffat S (2004) Solution structure of synthetic 21mer peptide spanning region 135–155 (in human numbering) of sheep prion protein http://www.pdb.org/pdb/explore/explore.do?structureId=1S4T

  • Kuwata K, Li H, Yamada H, Legname G, Prusiner SB, Akasaka K, James TL (2002) Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrPSc? Biochemistry 41:12277–12283

    PubMed  CAS  Google Scholar 

  • Latarjet R, Muel B, Haig DA, Clarke MC, Alper T (1970) Inactivation of the scrapie agent by near monochromatic ultraviolet light. Nature 227:1341–1343

    PubMed  CAS  Google Scholar 

  • Lee S, Antony L, Hartmann R, Knaus KJ, Surewicz K, Surewicz WK, Yee VC (2010) Conformational diversity in prion protein variants influences intermolecular β-sheet formation. EMBO J 29:251–262

    PubMed  CAS  Google Scholar 

  • Legname G, Baskakov IV, Nguyen HO, Riesner D, Cohen FE, Dearmond SJ, Prusiner SB (2004) Synthetic mammalian prions. Science 305:673–676

    PubMed  CAS  Google Scholar 

  • Legname G, Nguyen HO, Baskakov IV, Cohen FE, Dearmond SJ, Prusiner SB (2005) Strain-specified characteristics of mouse synthetic prions. Proc Natl Acad Sci USA 102:2168–2173

    PubMed  CAS  Google Scholar 

  • Legname G, Nguyen HO, Peretz D, Cohen FE, Dearmond SJ, Prusiner SB (2006) Continuum of prion protein structures enciphers a multitude of prion isolate-specified phenotypes. Proc Natl Acad Sci USA 103:19105–19110

    PubMed  CAS  Google Scholar 

  • Li J, Mei FH, Xiao GF, Guo CY, Lin DH (2007) 1H, 13C and 15N resonance assignments of rabbit prion protein (91–228). J Biomol NMR 38:181

    PubMed  CAS  Google Scholar 

  • Liemann S, Glockshuber R (1999) Influence of amino acid substitutions related to inherited human prion diseases on the thermodynamic stability of the cellular prion protein. Biochemistry 38:3258–3267

    PubMed  CAS  Google Scholar 

  • Liu H, Farr-Jones S, Ulyanov NB, Llinas M, Marqusee S, Groth D, Cohen FE, Prusiner SB, James TL (1999) Solution structure of Syrian hamster prion protein rPrP(90–231). Biochemistry 38:5362–5377

    PubMed  CAS  Google Scholar 

  • Lopez Garcia F, Zahn R, Riek R, Wuthrich K (2000) NMR structure of the bovine prion protein. Proc Natl Acad Sci USA 97:8334–8339

    PubMed  CAS  Google Scholar 

  • Lysek DA, Schorn C, Nivon LG, Esteve-Moya V, Christen B, Calzolai L, Von Schroetter C, Fiorito F, Herrmann T, Guntert P, Wuthrich K (2005) Prion protein NMR structures of cats, dogs, pigs, and sheep. Proc Natl Acad Sci USA 102:640–645

    PubMed  CAS  Google Scholar 

  • Maddelein ML, Dos Reis S, Duvezin-Caubet S, Coulary-Salin B, Saupe SJ (2002) Amyloid aggregates of the HET-s prion protein are infectious. Proc Natl Acad Sci USA 99:7402–7407

    PubMed  CAS  Google Scholar 

  • Manuelidis L, Fritch W (1996) Infectivity and host responses in Creutzfeldt–Jakob disease. Virology 216:46–59

    PubMed  CAS  Google Scholar 

  • Mashima T, Matsugami A, Nishikawa F, Nishikawa S, Katahira M (2009) Unique quadruplex structure and interaction of an RNA aptamer against bovine prion protein. Nucleic Acids Res 37:6249–6258

    PubMed  CAS  Google Scholar 

  • Mckinley MP, Bolton DC, Prusiner SB (1983) A protease-resistant protein is a structural component of the scrapie prion. Cell 35:57–62

    PubMed  CAS  Google Scholar 

  • Mckinley MP, Meyer RK, Kenaga L, Rahbar F, Cotter R, Serban A, Prusiner SB (1991a) Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis. J Virol 65:1340–1351

    PubMed  CAS  Google Scholar 

  • Mckinley MP, Taraboulos A, Kenaga L, Serban D, Stieber A, Dearmond SJ, Prusiner SB, Gonatas N (1991b) Ultrastructural localization of scrapie prion proteins in cytoplasmic vesicles of infected cultured cells. Lab Invest 65:622–630

    PubMed  CAS  Google Scholar 

  • Megy S, Bertho G, Kozin SA, Debey P, Hoa GH, Girault JP (2004) Possible role of region 152–156 in the structural duality of a peptide fragment from sheep prion protein. Protein Sci 13:3151–3160

    PubMed  CAS  Google Scholar 

  • Meyer RK, Mckinley MP, Bowman KA, Braunfeld MB, Barry RA, Prusiner SB (1986) Separation and properties of cellular and scrapie prion proteins. Proc Natl Acad Sci USA 83:2310–2314

    PubMed  CAS  Google Scholar 

  • Mills NL, Surewicz K, Surewicz WK, Sonnichsen FD (2009) Residue 129 polymorphism and conformational dynamics of familial prion diseases associated with the human prion protein variant D178N. doi:10.2210/pdb2k1d/pdb http://www.pdb.org/pdb/explore/explore.do?structureId=2K1D

  • Mishra RS, Bose S, Gu Y, Li R, Singh N (2003) Aggresome formation by mutant prion proteins: the unfolding role of proteasomes in familial prion disorders. J Alzheimers Dis 5:15–23

    PubMed  CAS  Google Scholar 

  • Muramoto T, Dearmond SJ, Scott M, Telling GC, Cohen FE, Prusiner SB (1997) Heritable ­disorder resembling neuronal storage disease in mice expressing prion protein with deletion of an α-helix. Nat Med 3:750–755

    PubMed  CAS  Google Scholar 

  • Nguyen JT, Inouye H, Baldwin MA, Fletterick RJ, Cohen FE, Prusiner SB, Kirschner DA (1995) X-ray diffraction of scrapie prion rods and PrP peptides. J Mol Biol 252:412–422

    PubMed  CAS  Google Scholar 

  • Novitskaya V, Makarava N, Bellon A, Bocharova OV, Bronstein IB, Williamson RA, Baskakov IV (2006) Probing the conformation of the prion protein within a single amyloid fibril using a novel immunoconformational assay. J Biol Chem 281:15536–15545

    PubMed  CAS  Google Scholar 

  • Onisko B, Fernandez EG, Freire ML, Schwarz A, Baier M, Camina F, Garcia JR, Rodriguez-Segade Villamarin S, Requena JR (2005) Probing PrPSc structure using chemical cross-linking and mass spectrometry: Evidence of the proximity of Gly90 amino termini in the PrP 27–30 aggregate. Biochemistry 44:10100–10109

    PubMed  CAS  Google Scholar 

  • Palmer MS, Dryden AJ, Hughes JT, Collinge J (1991) Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease. Nature 352:340–342

    PubMed  CAS  Google Scholar 

  • Pan K-M, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, Mehlhorn I, Huang Z, Fletterick RJ, Cohen FE, Prusiner SB (1993) Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci USA 90:10962–10966

    PubMed  CAS  Google Scholar 

  • Parchi P, Zou W, Wang W, Brown P, Capellari S, Ghetti B, Kopp N, Schulz-Schaeffer WJ, Kretzschmar HA, Head MW, Ironside JW, Gambetti P, Chen SG (2000) Genetic influence on the structural variations of the abnormal prion protein. Proc Natl Acad Sci USA 97:10168–10172

    PubMed  CAS  Google Scholar 

  • Peretz D, Williamson RA, Matsunaga Y, Serban H, Pinilla C, Bastidas RB, Rozenshteyn R, James TL, Houghten RA, Cohen FE, Prusiner SB, Burton DR (1997) A conformational transition at the N-terminus of the prion protein features in formation of the scrapie isoform. J Mol Biol 273:614–622

    PubMed  CAS  Google Scholar 

  • Perez DR, Damberger FF, Wuthrich K (2010) Horse prion protein NMR structure and comparisons with related variants of the mouse prion protein. J Mol Biol 400:121–128

    PubMed  CAS  Google Scholar 

  • Piccardo P, Dlouhy SR, Lievens PM, Young K, Bird TD, Nochlin D, Dickson DW, Vinters HV, Zimmerman TR, Mackenzie IR, Kish SJ, Ang LC, De Carli C, Pocchiari M, Brown P, Gibbs CJ Jr, Gajdusek DC, Bugiani O, Ironside J, Tagliavini F, Ghetti B (1998) Phenotypic variability of Gerstmann–Straüssler–Scheinker disease is associated with prion protein heterogeneity. J Neuropathol Exp Neurol 57:979–988

    PubMed  CAS  Google Scholar 

  • Premzl M, Delbridge M, Gready JE, Wilson P, Johnson M, Davis J, Kuczek E, Marshall Graves JA (2005) The prion protein gene: identifying regulatory signals using marsupial sequence. Gene 349:121–134

    PubMed  CAS  Google Scholar 

  • Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216:136–144

    PubMed  CAS  Google Scholar 

  • Prusiner SB (1997) Biology of prions. In: Rosenberg RN, Prusiner SB, Dimauro S, Barchi RL (eds) The molecular and genetic basis of neurological disease, 2nd edn. Butterworth Heinemann, Stoneham

    Google Scholar 

  • Prusiner SB (1998) Prions. Proc Natl Acad Sci USA 95:13363–13383

    PubMed  CAS  Google Scholar 

  • Prusiner SB, Scott MR, Dearmond SJ, Cohen FE (1998) Prion protein biology. Cell 93:337–348

    PubMed  CAS  Google Scholar 

  • Requena JR (2009) Structure of mammalian prions. Future Virol 4:295–307

    CAS  Google Scholar 

  • Riek R, Hornemann S, Wider G, Billeter M, Glockshuber R, Wüthrich K (1996) NMR structure of the mouse prion protein domain PrP(121–231). Nature 382:180–182

    PubMed  CAS  Google Scholar 

  • Ronga L, Palladino P, Saviano G, Tancredi T, Benedetti E, Ragone R, Rossi F (2008) Structural characterization of a neurotoxic threonine-rich peptide corresponding to the human prion protein α-2 helical 180–195 segment, and comparisonwith full length α2-helix-derived peptides. J. Pept. Sci. 14:1096–1102

    Google Scholar 

  • Sajnani G, Pastrana MA, Dynin I, Onisko B, Requena JR (2008) Scrapie prion protein structural constraints obtained by limited proteolysis and mass spectrometry. J Mol Biol 382:88–98

    PubMed  CAS  Google Scholar 

  • Sawaya MR, Sambashivan S, Nelson R, Ivanova MI, Sievers SA, Apostol MI, Thompson MJ, Balbirnie M, Wiltzius JJ, Mcfarlane HT, Madsen AO, Riekel C, Eisenberg D (2007) Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature 447:453–457

    PubMed  CAS  Google Scholar 

  • Sim VL, Caughey B (2009) Ultrastructures and strain comparison of under-glycosylated scrapie prion fibrils. Neurobiol Aging 30:2031–2042

    PubMed  CAS  Google Scholar 

  • Smirnovas V, Kim JI, Lu X, Atarashi R, Caughey B, Surewicz WK (2009) Distinct structures of scrapie prion protein (PrPSc)-seeded versus spontaneous recombinant prion protein fibrils revealed by hydrogen/deuterium exchange. J Biol Chem 284:24233–24241

    PubMed  CAS  Google Scholar 

  • Spassov S, Beekes M, Naumann D (2006) Structural differences between TSEs strains investigated by FT-IR spectroscopy. Biochim Biophys Acta 1760:1138–1149

    PubMed  CAS  Google Scholar 

  • Swietnicki W, Petersen RB, Gambetti P, Surewicz WK (1998) Familial mutations and the thermodynamic stability of the recombinant human prion protein. J Biol Chem 273:31048–31052

    PubMed  CAS  Google Scholar 

  • Taraboulos A, Raeber AJ, Borchelt DR, Serban D, Prusiner SB (1992) Synthesis and trafficking of prion proteins in cultured cells. Mol Biol Cell 3:851–863

    PubMed  CAS  Google Scholar 

  • Taubner LM, Bienkiewicz EA, Copie V, Caughey B (2010) Structure of the flexible amino-­terminal domain of prion protein bound to a sulfated glycan. J Mol Biol 395:475–490

    PubMed  CAS  Google Scholar 

  • Telling GC (2000) Prion protein genes and prion diseases: studies in transgenic mice. Neuropathol Appl Neurobiol 26:209–220

    PubMed  CAS  Google Scholar 

  • Telling GC, Scott M, Mastrianni J, Gabizon R, Torchia M, Cohen FE, Dearmond SJ, Prusiner SB (1995) Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83:79–90

    PubMed  CAS  Google Scholar 

  • Telling GC, Scott M, Prusiner SB (1996) Deciphering prion diseases with transgenic mice. In: Gibbs CJ Jr (ed) Bovine spongiform encephalopathy: the BSE dilemma. Springer Verlag, New York

    Google Scholar 

  • Vanik DL, Surewicz WK (2002) Disease-associated F198S mutation increases the propensity of the recombinant prion protein for conformational conversion to scrapie-like form. J Biol Chem 277:49065–49070

    PubMed  CAS  Google Scholar 

  • Vey M, Pilkuhn S, Wille H, Nixon R, Dearmond SJ, Smart EJ, Anderson RG, Taraboulos A, Prusiner SB (1996) Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains. Proc Natl Acad Sci USA 93:14945–14949

    PubMed  CAS  Google Scholar 

  • Viles JH, Cohen FE, Prusiner SB, Goodin DB, Wright PE, Dyson HJ (1999) Copper binding to the prion protein: structural implications of four identical cooperative binding sites. Proc Natl Acad Sci USA 96:2042–2047

    PubMed  CAS  Google Scholar 

  • Viles JH, Donne D, Kroon G, Prusiner SB, Cohen FE, Dyson HJ, Wright PE (2001) Local structural plasticity of the prion protein. Analysis of NMR relaxation dynamics. Biochemistry 40:2743–2753

    PubMed  CAS  Google Scholar 

  • Wasmer C, Lange A, Van Melckebeke H, Siemer AB, Riek R, Meier BH (2008) Amyloid fibrils of the HET-s(218–289) prion form a β solenoid with a triangular hydrophobic core. Science 319:1523–1526

    PubMed  CAS  Google Scholar 

  • Wen Y, Li J, Yao W, Xiong M, Hong J, Peng Y, Xiao G, Lin D (2010) Unique structural characteristics of the rabbit prion protein. J Biol Chem 285(41):31682–31693

    PubMed  CAS  Google Scholar 

  • Wille H, Michelitsch MD, Guenebaut V, Supattapone S, Serban A, Cohen FE, Agard DA, Prusiner SB (2002) Structural studies of the scrapie prion protein by electron crystallography. Proc Natl Acad Sci USA 99:3563–3568

    PubMed  CAS  Google Scholar 

  • Wille H, Govaerts C, Borovinskiy A, Latawiec D, Downing KH, Cohen FE, Prusiner SB (2007) Electron crystallography of the scrapie prion protein complexed with heavy metals. Arch Biochem Biophys 467:239–248

    PubMed  CAS  Google Scholar 

  • Wille H, Bian W, Mcdonald M, Kendall A, Colby DW, Bloch L, Ollesch J, Borovinskiy AL, Cohen FE, Prusiner SB, Stubbs G (2009) Natural and synthetic prion structure from X-ray fiber ­diffraction. Proc Natl Acad Sci USA 106:16990–16995

    PubMed  CAS  Google Scholar 

  • Williamson RA, Peretz D, Pinilla C, Ball H, Bastidas RB, Rozenshteyn R, Houghten RA, Prusiner SB, Burton DR (1998) Mapping the prion protein using recombinant antibodies. J Virol 72:9413–9418

    PubMed  CAS  Google Scholar 

  • Wiltzius JJ, Landau M, Nelson R, Sawaya MR, Apostol MI, Goldschmidt L, Soriaga AB, Cascio D, Rajashankar K, Eisenberg D (2009) Molecular mechanisms for protein-encoded inheritance. Nat Struct Mol Biol 16:973–978

    PubMed  CAS  Google Scholar 

  • Windl O, Dempster M, Estibeiro JP, Lathe R, De Silva R, Esmonde T, Will R, Springbett A, Campbell TA, Sidle KC, Palmer MS, Collinge J (1996) Genetic basis of Creutzfeldt–Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene. Hum Genet 98:259–264

    PubMed  CAS  Google Scholar 

  • Wopfner F, Weidenhofer G, Schneider R, Von Brunn A, Gilch S, Schwarz TF, Werner T, Schatzl HM (1999) Analysis of 27 mammalian and 9 avian PrPs reveals high conservation of flexible regions of the prion protein. J Mol Biol 289:1163–1178

    PubMed  CAS  Google Scholar 

  • Worrall BB, Herman ST, Capellari S, Lynch T, Chin S, Gambetti P, Parchi P (1999) Type 1 ­protease resistant prion protein and valine homozygosity at codon 129 of PRNP identify a subtype of sporadic Creutzfeldt–Jakob disease. J Neurol Neurosurg Psychiatry 67:671–674

    PubMed  CAS  Google Scholar 

  • Young K, Piccardo P, Kish SJ, Ang LC, Dlouhy S, Ghetti B (1998) Gerstmann–Sträussler–Scheinker disease (GSS) with a mutation at prion protein (PrP) residue 212. J Neuropathol Exp Neurol 57:518

    Google Scholar 

  • Zahn R (2003) The octapeptide repeats in mammalian prion protein constitute a pH-dependent folding and aggregation site. J Mol Biol 334:477–488

    PubMed  CAS  Google Scholar 

  • Zahn R, Von Schroetter C, Wuthrich K (1997) Human prion proteins expressed in Escherichia coli and purified by high-affinity column refolding. FEBS Lett 417:400–404

    PubMed  CAS  Google Scholar 

  • Zahn R, Liu A, Luhrs T, Riek R, Von Schroetter C, Lopez Garcia F, Billeter M, Calzolai L, Wider G, Wuthrich K (2000) NMR solution structure of the human prion protein. Proc Natl Acad Sci USA 97:145–150

    PubMed  CAS  Google Scholar 

  • Zahn R, Guntert P, Von Schroetter C, Wuthrich K (2003) NMR structure of a variant human prion protein with two disulfide bridges. J Mol Biol 326:225–234

    PubMed  CAS  Google Scholar 

  • Zanusso G, Farinazzo A, Prelli F, Fiorini M, Gelati M, Ferrari S, Righetti PG, Rizzuto N, Frangione B, Monaco S (2004) Identification of distinct N-terminal truncated forms of prion protein in different Creutzfeldt–Jakob disease subtypes. J Biol Chem 279:38936–38942

    PubMed  CAS  Google Scholar 

  • Zhang Y, Swietnicki W, Zagorski MG, Surewicz WK, Sonnichsen FD (2000) Solution structure of the E200K variant of human prion protein. Implications for the mechanism of pathogenesis in familial prion diseases. J Biol Chem 275:33650–33654

    PubMed  CAS  Google Scholar 

  • Zimmermann K, Turecek PL, Schwarz HP (1999) Genotyping of the prion protein gene at codon 129. Acta Neuropathol 97:355–358

    PubMed  CAS  Google Scholar 

  • Zou WQ, Capellari S, Parchi P, Sy MS, Gambetti P, Chen SG (2003) Identification of novel ­proteinase K-resistant C-terminal fragments of PrP in Creutzfeldt–Jakob disease. J Biol Chem 278:40429–40436

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Cedric Govaerts for kindly providing Fig. 9.1, and Gabriella Furlan for editing and proofreading the manuscript.

Author information

Authors and Affiliations

  1. Scuola Internazionale Superiore di Studi Avanzati (SISSA), via Bonomea 265, I-34136, Trieste, Italy

    Giuseppe Legname, Gabriele Giachin & Federico Benetti

Authors
  1. Giuseppe Legname
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriele Giachin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Federico Benetti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuseppe Legname .

Editor information

Editors and Affiliations

  1. , Research School of Biology, Australian National University, Linnaeus Way, Canberra, 0200, Aust Capital Terr, Australia

    Farid Rahimi

  2. , Neurology, University of California at Los Angeles, Charles E. Young Drive South 635, Los Angeles, 90095-7334, California, USA

    Gal Bitan

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Legname, G., Giachin, G., Benetti, F. (2012). Structural Studies of Prion Proteins and Prions. In: Rahimi, F., Bitan, G. (eds) Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2774-8_9

Download citation

Publish with us

Policies and ethics

Search

Navigation