Summary
Molecular chaperones are proteins involved in the folding of other proteins. Among these chaperones, some are involved in their own folding (auto-chaperones). A question arises: what is the mechanism of the chaperone folding catalysis? A model for protein folding that uses the thermodynamics of irreversible processes and statistical mechanics to describe the phenomenon is proposed; the analysis presents a clear link between these two aspects. A consequence of this model is the possible existence of misfolded proteins. This point is discussed and some experimental results arguing in this direction detailed. This thermo-kinetic model is applied to protein folding driven by a molecular chaperone. Analysis of folding shows that a misfolded chaperone can induce mis-folding in protein and, in the case of autofolding (auto-chaperone), may lead to new misfolded chaperones. The consequences are explored by computer simulations. They show that such an auto-chaperone could behave as a new kind of informative molecule and replicate a misfolded structure by a process similar to infection. A quantitative model, displaying the epidemiologic characters of prion infections, is derived from this hypothesis. This hypothesis satisfactorily explains the three manifestations (infectious, genetic and sporadic) that are the characteristic features of all prion diseases. Are prions really molecular chaperones required for their own assembly? Analysis of the structure of prions revealed some features shared by true molecular chaperones. This analysis suggests the positions of the mutations likely to lead to the characteristic early onset of encephalopathy. They are in good agreement with experimental results.
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References
Almeida MR, Longo AI, Sakaki H, Costa PP, Saraiva MJM (1990) Prenatal diagnostic of familial amyloidotic neuropathy. Hum Genet 85: 623–626
Baker D, Sohl J, Agard DA (1992) A protein-folding reaction under kinetic control. Nature 356: 263–265
Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987) Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329: 506–512
Brooks C, Karplus M, Pettitt M (1988) Proteins: a theoretical perspective of dynamics, structure, and thermodynamics. Wiley, New York
Buchner J, Schmidt M, Fuchs M, Jaenicke R, Rudolph R, Schmid FX, Kiefhaber T (1991) GroE facilitates refolding of citrate synthase by suppressing aggregation. Biochemistry 30: 1586–1591
Büeler H, Fischer M, Lang Y, Bluethmann H, Lipp H-P, DeArmond SJ, Prusiner SB, Aguet M, Weissmann C (1992) Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356: 577–582
Bycroft M, Matouschek A, Kellis JT, Serrano L, Fersht AR (1990) Detection and characterization of a folding intermediate in barnase by RMN. Nature 346: 488–490
Carlson GA, Hsiao K, Oesch B, Westaway D, Prusiner SB (1991) Genetics of prion infections. Trends Genet 7: 61–65
Cheng MY, Hartl F-U, Horwich AI (1990) The mitochondrial chaperonin hsp60 is required for its own assembly. Nature 348: 455–458
Chou PY, Fasman G (1974) Conformational parameters for amino acids in helical, 13-sheet, and random coil regions calculated from proteins. Biochemistry 13: 211–245
Degen E, Williams D (1991) Participation of a novel 88-kD protein in the biogenesis of murine Class I histocompatibility molecules. J Cell Biol 112: 1099–1115
Eisenberg D, Weiss RM, Terwilliger TC (1982) The helical hydrophobic moment a measure of the amphilicity of a helix. Nature 299: 371–374
Elis RJ (1987) Proteins as molecular chaperones. Nature 328: 378–379
Flaherty KM, DeLuca-Flaherty C, McKay DB (1990) Three-dimensional structure of the ATPase fragment of a 70K heat-shock cognate protein. Nature 346: 623–628
Gamier J, Osguthorpe DJ, Robson B (1978) Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol 120: 97–120
Gething M-J, Sambrook J (1992) Protein folding in the cell. Nature 355: 33–45
Georgopoulos C (1992) The emergence of the chaperone machines. Trends Biochem Sci 17: 295–299
Ghelis C, Yon J (1982) Protein folding. Academic Press, New York
Gibrat JF, Gamier J, Robson B (1987) Further develoments of protein secondary structure prediction using information theory. New parameters and consideration of residue pairs. J Mol Biol 198: 425–443
Grateau G (1992) Les amylose héréditaires. Medecine/Sciences 6: 524–531
Jou D, Llebot JE (1991) Introduction a la thermodynamique des processus biologiques. Techniques & Documentation-Lavoisier, Paris
Katchalsky A, Curran PF (1965) Nonequilibrium thermodynamics in biophysics. Harvard University Press, Cambridge Massachussets
Kim PS, Baldwin RL (1990) Intermediates in the folding reactions of small proteins. Annu Rev Biochem 59: 631–660
Landry SJ, Gierasch LM (1991) The chaperonin GroEL binds a polypeptide in an alpha-helical conformation. Biochemistry 307: 359–7362
Landry SJ, Jordan R, McMachen R, Gierash L (1992) Different conformation for the same polypeptide bound the chaperone DnaK and GroEL. Nature 355: 455–457
Liautard JP (1990) A thermo-kinetic model for protein folding. CR Acad Sci 311: 385–389
Liautard JP (1991) Are prions misfolded molecular chaperones? FEBS Lett 294: 155–157
Liautard JP (1991) Are prions misfolded molecular chaperones? FEBS Lett 294: 155–157
Matthews RC (1991) The mechanism of protein folding. Curr Opin Struct Biol 1: 28–35
Maury CPJ (1990) β-microglobulin amyloidosis. Rheumatol Int 10: 1–8
McLachlan AD (1976) Periodic fearures in the amino acid sequence of nematode myosin rod. J Mol Biol 103: 271–298
Osterman J, Horwich AL, Neupert W, Hartl F-U (1989) Protein folding in mitochondria requires complex formation with hsp60 and ATP hydrolysis. Nature 341: 125–130
Prigogine I (1968) Introduction à la thermodynamique des processus irreversibles. Dunod, Paris
Prusiner SB, Groth DF, Bolton DC, Kent SB, Hood LE (1984) Purification and structural studies of a major scrapie prion protein. Cell 38: 127–134
Prusiner SB, Scott M, Foster D, Pan KM, Groth D, Mirenda C, Torchia M, Yang SL, Serban D, Carlson GA, Hoppe PC, Westaway D, DeArmond SJ (1990) Transgenic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63: 673–686
Ptitsyn OB, Pain RH, Semisotnov GV, Zerovnik E, Razguliaev OI (1990) Evidence for molten-globule state as a general intermediate in protein folding. FEBS Lett 262: 20–24
Rippmann F, Taylor WR, Rothbard JB, Green M (1991) A hypothetical model for the peptide binding domain of hsp70 based on the peptide binding domain of HLA. EMBO J 10: 1053–1059
Schmid FX (1991) Catalysis and assistance of protein folding. Curr Opin Struct Biol 1: 36–41
Stahl N, Borchelt DR, Hsiao K, Prusiner S (1987) Scrapie prion protein contain a phosphatidylinositol glycopipid. Cell 51: 229–240
Sugawara T, Kuwajima K, Sugai S (1991) Folding of staphylococcal nuclease A studied by equilibrium and kinetic circular dichroism spectra. Biochemistry 30: 2698–2706
Vitanen PV, Lubben TH, Goloubinoff P, O’Keefe PO, Lorimer GH (1990) Chaperonin-facilited refolding of ribulose-bisphosphate carboxylase and ATP hydrolysis by chaperonin 60 ( GroEL) are K+-dependent. Biochemistry 29: 5665–5671
Weissmann H. (1991) A “unified theory” of prion propagation. Nature 352: 679–683
Wiech H, Buchner J, Zimmermann R, Jakob U (1992) Hsp90 chaperones protein folding in vitro. Nature 358: 169–170
Zimm BH, Bragg JK (1959) Theory of the phase transition between helix and random coil in polypeptide chains. J Chem Phys 31: 526–532
Zhu X, Ohta Y, Jordan F, Inouye M (1989) Pro-sequence of subtilisin can guide the refolding of denatured subtilisin in an intermolecular process. Nature 339: 483–484
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© 1993 Springer-Verlag
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Liautard, JP. (1993). Prions and molecular chaperones. In: Kaaden, OR., Eichhorn, W., Czerny, CP. (eds) Unconventional Agents and Unclassified Viruses. Archives of Virology, vol 7. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9300-6_18
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DOI: https://doi.org/10.1007/978-3-7091-9300-6_18
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-82480-1
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