Biophysical Reviews

, Volume 10, Issue 2, pp 493–502 | Cite as

Salt-induced formations of partially folded intermediates and amyloid fibrils suggests a common underlying mechanism

  • Yuji Goto
  • Masayuki Adachi
  • Hiroya Muta
  • Masatomo So
Review
  • 135 Downloads

Abstract

Amyloid fibrils are misfolded forms of proteins and are involved in various diseases. They have been studied extensively with the aim to obtain a comprehensive understanding of protein folding and misfolding and to use this knowledge to develop therapeutic strategies against the associated diseases. Salt conditions are important factors determining the formation and stability of amyloid fibrils. In the 1990s, salt effects were studied extensively to understand the conformational stability of acid-denatured proteins, and the results of these studies revealed the role of electrostatic repulsion in forming the compact intermediate states. In this review, we compare the effects of salts on the compact intermediate states with those on the formation of amyloid fibrils under acidic conditions. The results argue that both protein folding and misfolding are driven by the same forces, although the resultant conformations are distinct because they are monomeric and multimeric reactions, respectively.

Keywords

Amyloid fibril Amorphous aggregation Molten globule Protein folding/misfolding Salt effects Supersaturation 

Notes

Acknowledgements

This work was supported by JSPS KAKENHI Grant Numbers 15H04362, 15 K14458, and 16H00836 and 17H06352, and by the SENTAN from Japan Agency for Medical Research and Development (AMED).

Compliance with ethical standards

Conflict of interest

Yuji Goto declares that he has no conflicts of interest. Masayuki Adachi declares that he has no conflicts of interest. Hiroya Muta declares that he has no conflicts of interest. Masatomo So declares that he has no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Adachi M, So M, Sakurai K, Kardos J, Goto Y (2015) Supersaturation-limited and unlimited phase transitions compete to produce the pathway complexity in amyloid fibrillation. J Biol Chem 290:18134–18145Google Scholar
  2. Arai M, Kuwajima K (2000) Role of the molten globule state in protein folding. Adv Protein Chem 53:209–282CrossRefPubMedGoogle Scholar
  3. Arakawa T, Timasheff SN (1982) Preferential interactions of proteins with salts in concentrated solutions. Biochemistry 21:6545–6552CrossRefPubMedGoogle Scholar
  4. Bemporad F, Chiti F (2012) Protein misfolded oligomers: experimental approaches, mechanism of formation, and structure-toxicity relationships. Chem Biol 19:315–327CrossRefPubMedGoogle Scholar
  5. Bergfors T (2003) Seeds to crystals. J Struct Biol 142:66–76CrossRefPubMedGoogle Scholar
  6. Chatani E, Goto Y (2005) Structural stability of amyloid fibrils of β2-microglobulin in comparison with its native fold. Biochim Biophys Acta 1753:64–75Google Scholar
  7. Chatani E, Lee YH, Yagi H, Yoshimura Y, Naiki H, Goto Y (2009) Ultrasonication-dependent production and breakdown lead to minimum-sized amyloid fibrils. Proc Natl Acad Sci USA106:11119–11124Google Scholar
  8. Ciryam P, Kundra R, Morimoto RI, Dobson CM, Vendruscolo M (2013) Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins. Cell Rep 5:781–790Google Scholar
  9. Ciryam P, Tartaglia GG, Morimoto RI, Dobson CM, Vendruscolo M (2015) Supersaturation is a major driving force for protein aggregation in neurodegenerative diseases. Trends Pharmacol Sci 36:72–77Google Scholar
  10. Cohlberg JA, Li J, Uversky VN, Fink AL (2002) Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from α-synuclein in vitro. Biochemistry 41:1502–1511Google Scholar
  11. Colvin MT, Silvers R, Ni QZ et al (2016) Atomic resolution structure of monomorphic Aβ(1-42) amyloid fibrils. J Am Chem Soc 138:9663–9674Google Scholar
  12. Coquerel G (2014) Crystallization of molecular systems from solution: phase diagrams, supersaturation and other basic concepts. Chem Soc Rev 43:2286–2300CrossRefPubMedGoogle Scholar
  13. Dobson CM (2003) Protein folding and misfolding. Nature 426:884–890CrossRefPubMedGoogle Scholar
  14. Doig AJ, Derreumaux P (2015) Inhibition of protein aggregation and amyloid formation by small molecules. Curr Opin Struct Biol 30:50–56CrossRefPubMedGoogle Scholar
  15. Eisenberg D, Jucker M (2012) The amyloid state of proteins in human diseases. Cell 148:1188–1203CrossRefPubMedPubMedCentralGoogle Scholar
  16. Fink AL, Calciano LJ, Goto Y, Kurotsu T, Palleros DR (1994) Classification of acid denaturation of proteins: intermediates and unfolded states. Biochemistry 33:12504–12511Google Scholar
  17. Fitzpatrick AWP, Falcon B, He S et al (2017) Cryo-EM structures of tau filaments from Alzheimer's disease. Nature 547:185–190Google Scholar
  18. Giehm L, Otzen DE (2010) Strategies to increase the reproducibility of protein fibrillization in plate reader assays. Anal Biochem 400:270–281CrossRefPubMedGoogle Scholar
  19. Goto Y, Aimoto S (1991) Anion and pH-dependent conformational transition of an amphiphilic polypeptide. J Mol Biol 218:387–396CrossRefPubMedGoogle Scholar
  20. Goto Y, Fink AL (1989) Conformational states of β-Lactamase - molten-globule states at acidic and alkaline ph with high salt. Biochemistry 28:945–952Google Scholar
  21. Goto Y, Fink AL (1990) Phase diagram for acidic conformational states of apomyoglobin. J Mol Biol 214:803–805CrossRefPubMedGoogle Scholar
  22. Goto Y, Calciano LJ, Fink AL (1990a) Acid-induced folding of proteins. Proc Natl Acad Sci USA USA87:573–577Google Scholar
  23. Goto Y, Takahashi N, Fink AL (1990b) Mechanism of acid-induced folding of proteins. Biochemistry 29:3480–3488CrossRefPubMedGoogle Scholar
  24. Hagihara Y, Kataoka M, Aimoto S, Goto Y (1992) Charge repulsion in the conformational stability of melittin. Biochemistry 31:11908–11914Google Scholar
  25. Hagihara Y, Aimoto S, Fink AL, Goto Y(1993) Guanidine hydrochloride-induced folding of proteins. J Mol Biol 231:180–184Google Scholar
  26. Hamada D, Kidokoro S, Fukada H, Takahashi K, Goto Y (1994) Salt-induced formation of the molten globule state of cytochrome c studied by isothermal titration calorimetry. Proc Natl Acad Sci USA 91:10325–10329Google Scholar
  27. Ikenoue T, Lee YH, Kardos J et al (2014) Heat of supersaturation-limited amyloid burst directly monitored by isothermal titration calorimetry. Proc Natl Acad Sci USA 111:6654–6659Google Scholar
  28. Jarrett JT, Lansbury PT Jr (1993) Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie? Cell 73:1055–1058CrossRefPubMedGoogle Scholar
  29. Jucker M, Walker LC (2013) Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501:45–51CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kardos J, Yamamoto K, Hasegawa K, Naiki H, Goto Y (2004) Direct measurement of the thermodynamic parameters of amyloid formation by isothermal titration calorimetry. J Biol Chem 279:55308–55314Google Scholar
  31. Levin A, Mason TO, Adler-Abramovich L et al (2014) Ostwald’s rule of stages governs structural transitions and morphology of dipeptide supramolecular polymers. Nat Commun 5:5219Google Scholar
  32. Lin Y, Lee YH, Yoshimura Y, Yagi H, Goto Y (2014) Solubility and supersaturation-dependent protein misfolding revealed by ultrasonication. Langmuir 30:1845–1854Google Scholar
  33. Linse S, Cabaleiro-Lago C, Xue WF et al (2007) Nucleation of protein fibrillation by nanoparticles. Proc Natl Acad Sci USA 104:8691–8696Google Scholar
  34. Miti T, Mulaj M, Schmit JD, Muschol M (2015) Stable, metastable, and kinetically trapped amyloid aggregate phases. Biomacromolecules 16:326–335Google Scholar
  35. Morris AM, Watzky MA, Finke RG (2009) Protein aggregation kinetics, mechanism, and curve-fitting: a review of the literature. Biochim Biophys Acta 1794:375–397CrossRefPubMedGoogle Scholar
  36. Munishkina LA, Henriques J, Uversky VN, Fink AL (2004) Role of protein-water interactions and electrostatics in alpha-synuclein fibril formation. Biochemistry 43:3289–3300Google Scholar
  37. Myers SL, Jones S, Jahn TR et al (2006) A systematic study of the effect of physiological factors on β2-microglobulin amyloid formation at neutral pH. Biochemistry 45:2311–2321Google Scholar
  38. Naiki H, Hashimoto N, Suzuki S, Kimura H, Nakakuki K, Gejyo F (1997) Establishment of a kinetic model of dialysis-related amyloid fibril extension in vitro. Amyloid 4:223–232Google Scholar
  39. Nakajima K, Ogi H, Adachi K et al (2016) Nucleus factory on cavitation bubble for amyloid β fibril. Sci Rep 6:22015Google Scholar
  40. Nishii I, Kataoka M, Goto Y (1995) Thermodynamic stability of the molten globule states of apomyoglobin. J Mol Biol 250:223–238CrossRefPubMedGoogle Scholar
  41. Nitani A, Muta H, Adachi M et al (2017) Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation. J Biol Chem. doi:  10.1074/jbc.M117.813097
  42. Ohgushi M, Wada A (1983) 'Molten-globule state': a compact form of globular proteins with mobile side-chains. FEBS Lett 164:21–24CrossRefPubMedGoogle Scholar
  43. Ohhashi Y, Kihara M, Naiki H, Goto Y (2005) Ultrasonication-induced amyloid fibril formation of β2-microglobulin. J Biol Chem 280:32843–32848Google Scholar
  44. Raman B, Chatani E, Kihara M et al (2005) Critical balance of electrostatic and hydrophobic interactions is required for β2-microglobulin amyloid fibril growth and stability. Biochemistry 44:1288–1299Google Scholar
  45. Sipe JD, Benson MD, Buxbaum JN et al (2014) Nomenclature 2014: Amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid 21:221–224Google Scholar
  46. So M, Yagi H, Sakurai K, Ogi H, Naiki H, Goto Y (2011) Ultrasonication-dependent acceleration of amyloid fibril formation. J Mol Biol 412:568–577Google Scholar
  47. So M, Ishii A, Hata Y, Yagi H, Naiki H, Goto Y (2015) Supersaturation-limited and unlimited phase spaces compete to produce maximal amyloid fibrillation near the critical micelle concentration of sodium dodecyl sulfate. Langmuir 31:9973–9982Google Scholar
  48. So M, Hall D, Goto Y (2016) Revisiting supersaturation as a factor determining amyloid fibrillation. Curr Opin Struct Biol 36:32–39CrossRefPubMedGoogle Scholar
  49. So M, Hata Y, Naiki H, Goto Y (2017) Heparin-induced amyloid fibrillation of β2 -microglobulin explained by solubility and a supersaturation-dependent conformational phase diagram. Protein Sci 26:1024–1036Google Scholar
  50. Stoppini M, Bellotti V (2015) Systemic amyloidosis: lessons from β2-microglobulin. J Biol Chem 290:9951–9958Google Scholar
  51. Suzuki M, Yokoyama K, Lee YH, Goto Y (2011) A two-step refolding of acid-denatured microbial transglutaminase escaping from the aggregation-prone intermediate. Biochemistry 50:10390–10398Google Scholar
  52. Suzuki M, Sakurai K, Lee YH, Ikegami T, Yokoyama K, Goto Y (2012) A back hydrogen exchange procedure via the acid-unfolded state for a large protein. Biochemistry 51:5564–5570Google Scholar
  53. Tanford C (1968) Protein denaturation. Adv Protein Chem 23:121–282CrossRefPubMedGoogle Scholar
  54. Tanford C (1970) Protein denaturation. C. Theoretical models for the mechanism of denaturation. Adv Protein Chem 24:1–95CrossRefPubMedGoogle Scholar
  55. Tycko R, Wickner RB (2013) Molecular structures of amyloid and prion fibrils: consensus versus controversy. Acc Chem Res 46:1487–1496CrossRefPubMedPubMedCentralGoogle Scholar
  56. Umemoto A, Yagi H, So M, Goto Y (2014) High-throughput analysis of the ultrasonication-forced amyloid fibrillation reveals the mechanism underlying the large fluctuation in the lag time. J Biol Chem 289:27290–27299Google Scholar
  57. Walti MA, Ravotti F, Arai H et al (2016) Atomic-resolution structure of a disease-relevant Aβ(1-42) amyloid fibril. Proc Natl Acad Sci USA 113:E4976–E4984Google Scholar
  58. Washabaugh MW, Collins KD (1986) The systematic characterization by aqueous column chromatography of solutes which affect protein stability. J Biol Chem 261:12477–12485PubMedGoogle Scholar
  59. Wetzel R (2006) Kinetics and thermodynamics of amyloid fibril assembly. Acc Chem Res 39:671–679CrossRefPubMedGoogle Scholar
  60. Yamamoto S, Gejyo F (2005) Historical background and clinical treatment of dialysis-related amyloidosis. Biochim Biophys Acta 1753:4–10CrossRefPubMedGoogle Scholar
  61. Yamamoto S, Yamaguchi I, Hasegawa K et al (2004) Glycosaminoglycans enhance the trifluoroethanol-induced extensionof β2-microglobulin-related amyloid fibrils at a neutral pH. J Am Soc Nephrol 15:126–133Google Scholar
  62. Yanagi K, Sakurai K, Yoshimura Y et al (2012) The monomer-seed interaction mechanism in the formation of the β2-microglobulin amyloid fibril clarified by solution NMR techniques. J Mol Biol 422:390–402Google Scholar
  63. Yoshimura Y, Lin YX, Yagi H et al (2012) Distinguishing crystal-like amyloid fibrils and glass-like amorphous aggregates from their kinetics of formation. Proc Natl Acad Sci USA 109:14446–14451Google Scholar
  64. Yoshimura Y, So M, Yagi H, Goto Y (2013) Ultrasonication: an efficient agitation for accelerating the supersaturation-limited amyloid fibrillation of proteins. Jpn J Appl Physics 52:01–08Google Scholar

Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Institute for Protein ResearchOsaka UniversityOsakaJapan

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