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Protein Misfolding in Lipid-Mimetic Environments

  • Vladimir N. UverskyEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 855)

Abstract

Among various cellular factors contributing to protein misfolding and subsequent aggregation, membranes occupy a special position due to the two-way relations between the aggregating proteins and cell membranes. On one hand, the unstable, toxic pre-fibrillar aggregates may interact with cell membranes, impairing their functions, altering ion distribution across the membranes, and possibly forming non-specific membrane pores. On the other hand, membranes, too, can modify structures of many proteins and affect the misfolding and aggregation of amyloidogenic proteins. The effects of membranes on protein structure and aggregation can be described in terms of the “membrane field” that takes into account both the negative electrostatic potential of the membrane surface and the local decrease in the dielectric constant. Water-alcohol (or other organic solvent) mixtures at moderately low pH are used as model systems to study the joint action of the local decrease of pH and dielectric constant near the membrane surface on the structure and aggregation of proteins. This chapter describes general mechanisms of structural changes of proteins in such model environments and provides examples of various proteins aggregating in the “membrane field” or in lipid-mimetic environments.

Keywords

Membrane field Lipid mimetic Intrinsically disordered protein Protein misfolding Protein aggregation Protein-membrane interaction 

Abbreviations

Amyloid-β

AFM

Atomic force microscopy

ANS

Anilino-8-napthalene sulfonate

CD

Circular dichroism

DMPC

Dimyristoyl phosphatidylcholine

DMPG

1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] sodium salt

DMPS

Dimyristoyl phosphatidylserine

EtOH

Ethanol

FTIR

Fourier transform infrared spectroscopy

HFiP

1,1,1,3,3,3-hexafluoro-2-propanol

HSA

Human serum albumin

IAPP

Islet amyloid polypeptide

IDP

Intrinsically disordered protein

IDPR

Intrinsically disordered protein region

LUV

Large unilamellar vesicle

MeOH

Methanol

nFGF-1

Newt acidic fibroblast growth factor

PA

1,2-dipalmitoyl-sn-glycero-3-phosphate

PC

1,2-dipalmitoyl-sn-glycero-3-phospho-choline

PE

1-palmitoyl-2-oleoyl-phosphoethano-lamine

PG

1,2- dipalmitoyl-sn-glycero-3-phospho-RAC-(1-glycerol)

PI

Phosphatidylinositol

PrOH

Propanol

PS

1-palmitoyl-2-oleoyl-phosphatidylserine

SUV

Small unilamellar vesicle

TFE

2,2,2-trifluoroethanol

ThT

Thioflavin T

Notes

Acknowledgements

This work was supported in part by a grant from Russian Science Foundation RSCF № 14-24-00131

References

  1. Ahmad A, Millett IS, Doniach S, Uversky VN, Fink AL (2003) Partially folded intermediates in insulin fibrillation. Biochemistry 42(39):11404–11416PubMedGoogle Scholar
  2. Ahmad A, Millett IS, Doniach S, Uversky VN, Fink AL (2004) Stimulation of insulin fibrillation by urea-induced intermediates. J Biol Chem 279(15):14999–15013PubMedGoogle Scholar
  3. Alexandrescu AT, Ng YL, Dobson CM (1994) Characterization of a trifluoroethanol-induced partially folded state of alpha-lactalbumin. J Mol Biol 235(2):587–599PubMedGoogle Scholar
  4. Ancsin JB (2003) Amyloidogenesis: historical and modern observations point to heparan sulfate proteoglycans as a major culprit. Amyloid 10(2):67–79PubMedGoogle Scholar
  5. Appleton DW, Sarkar B (1971) The absence of specific copper (II)-binding site in dog albumin. A comparative study of human and dog albumins. J Biol Chem 246(16):5040–5046PubMedGoogle Scholar
  6. Arakawa T, Goddette D (1985) The mechanism of helical transition of proteins by organic solvents. Arch Biochem Biophys 240(1):21–32PubMedGoogle Scholar
  7. Arunkumar AI, Kumar TK, Kathir KM, Srisailam S, Wang HM, Leena PS, Chi YH, Chen HC, Wu CH, Wu RT, Chang GG, Chiu IM, Yu C (2002) Oligomerization of acidic fibroblast growth factor is not a prerequisite for its cell proliferation activity. Protein Sci 11(5):1050–1061PubMedCentralPubMedGoogle Scholar
  8. Barrow CJ, Yasuda A, Kenny PT, Zagorski MG (1992) Solution conformations and aggregational properties of synthetic amyloid beta-peptides of Alzheimer’s disease. Analysis of circular dichroism spectra. J Mol Biol 225(4):1075–1093PubMedGoogle Scholar
  9. Bedford MT, Leder P (1999) The FF domain: a novel motif that often accompanies WW domains. Trends Biochem Sci 24(7):264–265PubMedGoogle Scholar
  10. Bellotti V, Mangione P, Stoppini M (1999) Biological activity and pathological implications of misfolded proteins. Cell Mol Life Sci 55(6–7):977–991PubMedGoogle Scholar
  11. Binolfi A, Theillet FX, Selenko P (2012) Bacterial in-cell NMR of human alpha-synuclein: a disordered monomer by nature? Biochem Soc Trans 40(5):950–954PubMedGoogle Scholar
  12. Bonet R, Ramirez-Espain X, Macias MJ (2008) Solution structure of the yeast URN1 splicing factor FF domain: comparative analysis of charge distributions in FF domain structures-FFs and SURPs, two domains with a similar fold. Proteins 73(4):1001–1009PubMedGoogle Scholar
  13. Bonini NM, Giasson BI (2005) Snaring the function of alpha-synuclein. Cell 123(3):359–361PubMedGoogle Scholar
  14. Breydo L, Uversky VN (2011) Role of metal ions in aggregation of intrinsically disordered proteins in neurodegenerative diseases. Metallomics 3(11):1163–1180PubMedGoogle Scholar
  15. Breydo L, Wu JW, Uversky VN (2012) Alpha-synuclein misfolding and Parkinson’s disease. Biochim Biophys Acta 2:261–285Google Scholar
  16. Bucciantini M, Giannoni E, Chiti F, Baroni F, Formigli L, Zurdo J, Taddei N, Ramponi G, Dobson CM, Stefani M (2002) Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416(6880):507–511PubMedGoogle Scholar
  17. Buck M (1998) Trifluoroethanol and colleagues: cosolvents come of age. Recent studies with peptides and proteins. Q Rev Biophys 31(3):297–355PubMedGoogle Scholar
  18. Buck M, Radford SE, Dobson CM (1993) A partially folded state of hen egg white lysozyme in trifluoroethanol: structural characterization and implications for protein folding. Biochemistry 32(2):669–678PubMedGoogle Scholar
  19. Bussell R Jr, Ramlall TF, Eliezer D (2005) Helix periodicity, topology, and dynamics of membrane-associated alpha-synuclein. Protein Sci 14(4):862–872PubMedCentralPubMedGoogle Scholar
  20. Bychkova VE, Dujsekina AE, Klenin SI, Tiktopulo EI, Uversky VN, Ptitsyn OB (1996) Molten globule-like state of cytochrome c under conditions simulating those near the membrane surface. Biochemistry 35(19):6058–6063PubMedGoogle Scholar
  21. Castillo V, Chiti F, Ventura S (2013) The N-terminal helix controls the transition between the soluble and amyloid states of an FF domain. PLoS One 8(3):e58297PubMedCentralPubMedGoogle Scholar
  22. Chen YG, Siddhanta A, Austin CD, Hammond SM, Sung TC, Frohman MA, Morris AJ, Shields D (1996) Phospholipase D stimulates release of nascent secretory vesicles from trans-Golgi network. J Cell Biol 138(3):495–504Google Scholar
  23. Chiti F, Webster P, Taddei N, Clark A, Stefani M, Ramponi G, Dobson CM (1999) Designing conditions for in vitro formation of amyloid protofilaments and fibrils. Proc Natl Acad Sci U S A 96(7):3590–3594PubMedCentralPubMedGoogle Scholar
  24. Clark A, Nilsson MR (2004) Islet amyloid: a complication of islet dysfunction or an aetiological factor in type 2 diabetes? Diabetologia 47(2):157–169PubMedGoogle Scholar
  25. Coles M, Bicknell W, Watson AA, Fairlie DP, Craik DJ (1998) Solution structure of amyloid beta-peptide(1–40) in a water-micelle environment. Is the membrane-spanning domain where we think it is? Biochemistry 37(31):11064–11077PubMedGoogle Scholar
  26. Daughdrill GW, Pielak GJ, Uversky VN, Cortese MS, Dunker AK (2005) Natively disordered proteins. In: Buchner J, Kiefhaber T (eds) Handbook of protein folding. Wiley-VCH, Weinheim, pp 271–353Google Scholar
  27. Davidson WS, Jonas A, Clayton DF, George JM (1998) Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem 273(16):9443–9449PubMedGoogle Scholar
  28. de Laureto PP, Tosatto L, Frare E, Marin O, Uversky VN, Fontana A (2006) Conformational properties of the SDS-bound state of alpha-synuclein probed by limited proteolysis: unexpected rigidity of the acidic C-terminal tail. Biochemistry 45(38):11523–11531PubMedGoogle Scholar
  29. Diaz MD, Berger S (2001) Preferential solvation of a tetrapeptide by trifluoroethanol as studied by intermolecular NOE. Magn Reson Chem 39(7):369–373Google Scholar
  30. Diaz MD, Fioroni M, Burger K, Berger S (2002) Evidence of complete hydrophobic coating of bombesin by trifluoroethanol in aqueous solution: an NMR spectroscopic and molecular dynamics study. Chemistry 8(7):1663–1669PubMedGoogle Scholar
  31. Dikiy I, Eliezer D (2012) Folding and misfolding of alpha-synuclein on membranes. Biochim Biophys Acta 1818(4):1013–1018PubMedCentralPubMedGoogle Scholar
  32. Dobson CM (1999) Protein misfolding, evolution and disease. Trends Biochem Sci 24(9):329–332PubMedGoogle Scholar
  33. Dobson CM (2001) The structural basis of protein folding and its links with human disease. Philos Trans R Soc Lond B Biol Sci 356(1406):133–145PubMedCentralPubMedGoogle Scholar
  34. Dosztanyi Z, Csizmok V, Tompa P, Simon I (2005) IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics 21(16):3433–3434PubMedGoogle Scholar
  35. Dufour E, Bertrand-Harb C, Haertle T (1993) Reversible effects of medium dielectric constant on structural transformation of beta-lactoglobulin and its retinol binding. Biopolymers 33(4):589–598PubMedGoogle Scholar
  36. Dufour E, Robert P, Bertrand D, Haertle T (1994) Conformation changes of beta-lactoglobulin: an ATR infrared spectroscopic study of the effect of pH and ethanol. J Protein Chem 13(2):143–149PubMedGoogle Scholar
  37. Dunker AK, Obradovic Z, Romero P, Garner EC, Brown CJ (2000) Intrinsic protein disorder in complete genomes. Genome Informatics Ser Workshop 11:161–171Google Scholar
  38. Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Ausio J, Nissen MS, Reeves R, Kang C, Kissinger CR, Bailey RW, Griswold MD, Chiu W, Garner EC, Obradovic Z (2001) Intrinsically disordered protein. J Mol Graph Model 19(1):26–59PubMedGoogle Scholar
  39. Dunker AK, Cortese MS, Romero P, Iakoucheva LM, Uversky VN (2005) Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J 272(20):5129–5148PubMedGoogle Scholar
  40. Dyson HJ, Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6(3):197–208PubMedGoogle Scholar
  41. Eliezer D, Kutluay E, Bussell R Jr, Browne G (2001) Conformational properties of alpha-synuclein in its free and lipid-associated states. J Mol Biol 307(4):1061–1073PubMedGoogle Scholar
  42. Endo T, Schatz G (1988) Latent membrane perturbation activity of a mitochondrial precursor protein is exposed by unfolding. EMBO J 7(4):1153–1158PubMedCentralPubMedGoogle Scholar
  43. Fan P, Bracken C, Baum J (1993) Structural characterization of monellin in the alcohol-denatured state by NMR: evidence for beta-sheet to alpha-helix conversion. Biochemistry 32(6):1573–1582PubMedGoogle Scholar
  44. Fauvet B, Fares MB, Samuel F, Dikiy I, Tandon A, Eliezer D, Lashuel HA (2012a) Characterization of semisynthetic and naturally Nalpha-acetylated alpha-synuclein in vitro and in intact cells: implications for aggregation and cellular properties of alpha-synuclein. J Biol Chem 287(34):28243–28262PubMedCentralPubMedGoogle Scholar
  45. Fauvet B, Mbefo MK, Fares MB, Desobry C, Michael S, Ardah MT, Tsika E, Coune P, Prudent M, Lion N, Eliezer D, Moore DJ, Schneider B, Aebischer P, El-Agnaf OM, Masliah E, Lashuel HA (2012b) Alpha-synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. J Biol Chem 287(19):15345–15364PubMedCentralPubMedGoogle Scholar
  46. Fezoui Y, Teplow DB (2002) Kinetic studies of amyloid beta-protein fibril assembly. Differential effects of alpha-helix stabilization. J Biol Chem 277(40):36948–36954PubMedGoogle Scholar
  47. Fink AL (1998) Protein aggregation: folding aggregates, inclusion bodies and amyloid. Fold Des 3(1):R9–R23PubMedGoogle Scholar
  48. Fioroni M, Diaz MD, Burger K, Berger S (2002) Solvation phenomena of a tetrapeptide in water/trifluoroethanol and water/ethanol mixtures: a diffusion NMR, intermolecular NOE, and molecular dynamics study. J Am Chem Soc 124(26):7737–7744PubMedGoogle Scholar
  49. Furukawa K, Matsuzaki-Kobayashi M, Hasegawa T, Kikuchi A, Sugeno N, Itoyama Y, Wang Y, Yao PJ, Bushlin I, Takeda A (2006) Plasma membrane ion permeability induced by mutant alpha-synuclein contributes to the degeneration of neural cells. J Neurochem 97(4):1071–1077PubMedGoogle Scholar
  50. Gasch A, Wiesner S, Martin-Malpartida P, Ramirez-Espain X, Ruiz L, Macias MJ (2006) The structure of Prp40 FF1 domain and its interaction with the Crn-TPR1 motif of Clf1 gives a new insight into the binding mode of FF domains. J Biol Chem 281(1):356–364PubMedGoogle Scholar
  51. Gast K, Siemer A, Zirwer D, Damaschun G (2001) Fluoroalcohol-induced structural changes of proteins: some aspects of cosolvent-protein interactions. Eur Biophys J 30(4):273–283PubMedGoogle Scholar
  52. Georgieva ER, Ramlall TF, Borbat PP, Freed JH, Eliezer D (2008) Membrane-bound alpha-synuclein forms an extended helix: long-distance pulsed ESR measurements using vesicles, bicelles, and rodlike micelles. J Am Chem Soc 130(39):12856–12857PubMedCentralPubMedGoogle Scholar
  53. Glenner GG, Wong CW (1984a) Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122(3):1131–1135PubMedGoogle Scholar
  54. Glenner GG, Wong CW (1984b) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120(3):885–890PubMedGoogle Scholar
  55. Glenner GG, Wong CW, Quaranta V, Eanes ED (1984) The amyloid deposits in Alzheimer’s disease: their nature and pathogenesis. Appl Pathol 2(6):357–369PubMedGoogle Scholar
  56. Goda S, Takano K, Yamagata Y, Nagata R, Akutsu H, Maki S, Namba K, Yutani K (2000) Amyloid protofilament formation of hen egg lysozyme in highly concentrated ethanol solution. Protein Sci 9(2):369–375PubMedCentralPubMedGoogle Scholar
  57. Gruber HJ, Low PS (1988) Interaction of amphiphiles with integral membrane proteins. I. Structural destabilization of the anion transport protein of the erythrocyte membrane by fatty acids, fatty alcohols, and fatty amines. Biochim Biophys Acta 944(3):414–424PubMedGoogle Scholar
  58. Grudzielanek S, Jansen R, Winter R (2005) Solvational tuning of the unfolding, aggregation and amyloidogenesis of insulin. J Mol Biol 351(4):879–894PubMedGoogle Scholar
  59. Guijarro JI, Sunde M, Jones JA, Campbell ID, Dobson CM (1998) Amyloid fibril formation by an SH3 domain. Proc Natl Acad Sci U S A 95(8):4224–4228PubMedCentralPubMedGoogle Scholar
  60. Haaning S, Radutoiu S, Hoffmann SV, Dittmer J, Giehm L, Otzen DE, Stougaard J (2008) An unusual intrinsically disordered protein from the model legume Lotus japonicus stabilizes proteins in vitro. J Biol Chem 283(45):31142–31152PubMedCentralPubMedGoogle Scholar
  61. Hamada D, Kuroda Y, Tanaka T, Goto Y (1995) High helical propensity of the peptide fragments derived from beta-lactoglobulin, a predominantly beta-sheet protein. J Mol Biol 254(4):737–746PubMedGoogle Scholar
  62. Hirota N, Mizuno K, Goto Y (1998) Group additive contributions to the alcohol-induced alpha-helix formation of melittin: implication for the mechanism of the alcohol effects on proteins. J Mol Biol 275(2):365–378PubMedGoogle Scholar
  63. Holley M, Eginton C, Schaefer D, Brown LR (2008) Characterization of amyloidogenesis of hen egg lysozyme in concentrated ethanol solution. Biochem Biophys Res Commun 373(1):164–168PubMedGoogle Scholar
  64. Hong D-P, Hoshino M, Kuboi R, Goto Y (1999) Clustering of fluorine-substituted alcohols as a factor responsible for their marked effects on proteins and peptides. J Am Chem Soc 121:8427–8433Google Scholar
  65. Jackson M, Mantsch HH (1992) Halogenated alcohols as solvents for proteins: FTIR spectroscopic studies. Biochim Biophys Acta 1118(2):139–143PubMedGoogle Scholar
  66. Jakes R, Spillantini MG, Goedert M (1994) Identification of two distinct synucleins from human brain. FEBS Lett 345(1):27–32PubMedGoogle Scholar
  67. Jao CC, Der-Sarkissian A, Chen J, Langen R (2004) Structure of membrane-bound alpha-synuclein studied by site-directed spin labeling. Proc Natl Acad Sci U S A 101(22):8331–8336PubMedCentralPubMedGoogle Scholar
  68. Jao CC, Hegde BG, Chen J, Haworth IS, Langen R (2008) Structure of membrane-bound alpha-synuclein from site-directed spin labeling and computational refinement. Proc Natl Acad Sci U S A 105(50):19666–19671PubMedCentralPubMedGoogle Scholar
  69. Jenco JM, Rawlingson A, Daniels B, Morris AJ (1998) Regulation of phospholipase D2: selective inhibition of mammalian phospholipase D isoenzymes by alpha- and beta-synucleins. Biochemistry 37(14):4901–4909PubMedGoogle Scholar
  70. Jimenez JL, Guijarro JI, Orlova E, Zurdo J, Dobson CM, Sunde M, Saibil HR (1999) Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. EMBO J 18(4):815–821PubMedCentralPubMedGoogle Scholar
  71. Jimenez JL, Nettleton EJ, Bouchard M, Robinson CV, Dobson CM, Saibil HR (2002) The protofilament structure of insulin amyloid fibrils. Proc Natl Acad Sci U S A 99(14):9196–9201PubMedCentralPubMedGoogle Scholar
  72. Jo E, McLaurin J, Yip CM, St George-Hyslop P, Fraser PE (2000) Alpha-synuclein membrane interactions and lipid specificity. J Biol Chem 275(44):34328–34334PubMedGoogle Scholar
  73. Jo E, Fuller N, Rand RP, St George-Hyslop P, Fraser PE (2002) Defective membrane interactions of familial Parkinson’s disease mutant A30P alpha-synuclein. J Mol Biol 315(4):799–807PubMedGoogle Scholar
  74. Jones DT, Ward JJ (2003) Prediction of disordered regions in proteins from position specific score matrices. Proteins 53(Suppl 6):573–578PubMedGoogle Scholar
  75. Juarez J, Lopez SG, Cambon A, Taboada P, Mosquera V (2009) Influence of electrostatic interactions on the fibrillation process of human serum albumin. J Phys Chem B 113(30):10521–10529PubMedGoogle Scholar
  76. Kallberg Y, Gustafsson M, Persson B, Thyberg J, Johansson J (2001) Prediction of amyloid fibril-forming proteins. J Biol Chem 276(16):12945–12950PubMedGoogle Scholar
  77. Kelly JW (1998) The alternative conformations of amyloidogenic proteins and their multi-step assembly pathways. Curr Opin Struct Biol 8(1):101–106PubMedGoogle Scholar
  78. Kentsis A, Sosnick TR (1998) Trifluoroethanol promotes helix formation by destabilizing backbone exposure: desolvation rather than native hydrogen bonding defines the kinetic pathway of dimeric coiled coil folding. Biochemistry 37(41):14613–14622PubMedGoogle Scholar
  79. Khurana R, Gillespie JR, Talapatra A, Minert LJ, Ionescu-Zanetti C, Millett I, Fink AL (2001) Partially folded intermediates as critical precursors of light chain amyloid fibrils and amorphous aggregates. Biochemistry 40(12):3525–3535PubMedGoogle Scholar
  80. Kirkitadze MD, Condron MM, Teplow DB (2001) Identification and characterization of key kinetic intermediates in amyloid beta-protein fibrillogenesis. J Mol Biol 312(5):1103–1119PubMedGoogle Scholar
  81. Konno T, Oiki S, Morii T (2007) Synergistic action of polyanionic and non-polar cofactors in fibrillation of human islet amyloid polypeptide. FEBS Lett 581(8):1635–1638PubMedGoogle Scholar
  82. Kuprin S, Graslund A, Ehrenberg A, Koch MH (1995) Nonideality of water-hexafluoropropanol mixtures as studied by X-ray small angle scattering. Biochem Biophys Res Commun 217(3):1151–1156PubMedGoogle Scholar
  83. Lansbury PT Jr (1999) Evolution of amyloid: what normal protein folding may tell us about fibrillogenesis and disease. Proc Natl Acad Sci U S A 96(7):3342–3344PubMedCentralPubMedGoogle Scholar
  84. Lee HJ, Choi C, Lee SJ (2002) Membrane-bound alpha-synuclein has a high aggregation propensity and the ability to seed the aggregation of the cytosolic form. J Biol Chem 277(1):671–678PubMedGoogle Scholar
  85. Li X, Romero P, Rani M, Dunker AK, Obradovic Z (1999) Predicting protein disorder for N-, C-, and internal regions. Genome Informatics Ser Workshop 10:30–40Google Scholar
  86. Libich DS, Harauz G (2008) Solution NMR and CD spectroscopy of an intrinsically disordered, peripheral membrane protein: evaluation of aqueous and membrane-mimetic solvent conditions for studying the conformational adaptability of the 18.5 kDa isoform of myelin basic protein (MBP). Eur Biophys J 37(6):1015–1029PubMedGoogle Scholar
  87. Linding R, Jensen LJ, Diella F, Bork P, Gibson TJ, Russell RB (2003a) Protein disorder prediction: implications for structural proteomics. Structure 11(11):1453–1459PubMedGoogle Scholar
  88. Linding R, Russell RB, Neduva V, Gibson TJ (2003b) GlobPlot: exploring protein sequences for globularity and disorder. Nucleic Acids Res 31(13):3701–3708PubMedCentralPubMedGoogle Scholar
  89. Liu J, Rost B (2003) NORSp: predictions of long regions without regular secondary structure. Nucleic Acids Res 31(13):3833–3835PubMedCentralPubMedGoogle Scholar
  90. Madine J, Doig AJ, Middleton DA (2004) The aggregation and membrane-binding properties of an alpha-synuclein peptide fragment. Biochem Soc Trans 32(Pt 6):1127–1129PubMedGoogle Scholar
  91. Manning-Bog AB, McCormack AL, Li J, Uversky VN, Fink AL, Di Monte DA (2002) The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem 277(3):1641–1644PubMedGoogle Scholar
  92. Marinelli P, Castillo V, Ventura S (2013) Trifluoroethanol modulates amyloid formation by the all alpha-helical URN1 FF domain. Int J Mol Sci 14(9):17830–17844PubMedCentralPubMedGoogle Scholar
  93. Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8(8):2804–2815PubMedGoogle Scholar
  94. Marzban L, Park K, Verchere CB (2003) Islet amyloid polypeptide and type 2 diabetes. Exp Gerontol 38(4):347–351PubMedGoogle Scholar
  95. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A 82(12):4245–4249PubMedCentralPubMedGoogle Scholar
  96. McLean PJ, Kawamata H, Ribich S, Hyman BT (2000) Membrane association and protein conformation of alpha-synuclein in intact neurons. Effect of Parkinson’s disease-linked mutations. J Biol Chem 275(12):8812–8816PubMedGoogle Scholar
  97. Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ (1998) Alpha synuclein in neurodegenerative disorders: murderer or accomplice? Nat Med 4(7):755–757PubMedGoogle Scholar
  98. Middleton ER, Rhoades E (2010) Effects of curvature and composition on alpha-synuclein binding to lipid vesicles. Biophys J 99(7):2279–2288PubMedCentralPubMedGoogle Scholar
  99. Mihajlovic M, Lazaridis T (2008) Membrane-bound structure and energetics of alpha-synuclein. Proteins 70(3):761–778PubMedGoogle Scholar
  100. Moriarty GM, Janowska MK, Kang L, Baum J (2013) Exploring the accessible conformations of N-terminal acetylated alpha-synuclein. FEBS Lett 587(8):1128–1138PubMedCentralPubMedGoogle Scholar
  101. Munishkina LA, Phelan C, Uversky VN, Fink AL (2003) Conformational behavior and aggregation of alpha-synuclein in organic solvents: modeling the effects of membranes. Biochemistry 42(9):2720–2730PubMedGoogle Scholar
  102. Narizhneva NV, Uversky VN (1997) Human alpha-fetoprotein is in the molten globule state under conditions modelling protein environment near the membrane surface. Protein Pept Lett 4(4):243–249Google Scholar
  103. Nielsen L, Khurana R, Coats A, Frokjaer S, Brange J, Vyas S, Uversky VN, Fink AL (2001) Effect of environmental factors on the kinetics of insulin fibril formation: elucidation of the molecular mechanism. Biochemistry 40(20):6036–6046PubMedGoogle Scholar
  104. Nuscher B, Kamp F, Mehnert T, Odoy S, Haass C, Kahle PJ, Beyer K (2004) Alpha-synuclein has a high affinity for packing defects in a bilayer membrane: a thermodynamics study. J Biol Chem 279(21):21966–21975PubMedGoogle Scholar
  105. Oldfield CJ, Cheng Y, Cortese MS, Brown CJ, Uversky VN, Dunker AK (2005) Comparing and combining predictors of mostly disordered proteins. Biochemistry 44(6):1989–2000PubMedGoogle Scholar
  106. Otzen DE, Sehgal P, Nesgaard LW (2007) Alternative membrane protein conformations in alcohols. Biochemistry 46(14):4348–4359PubMedGoogle Scholar
  107. Pallares I, Vendrell J, Aviles FX, Ventura S (2004) Amyloid fibril formation by a partially structured intermediate state of alpha-chymotrypsin. J Mol Biol 342(1):321–331PubMedGoogle Scholar
  108. Pandey NK, Ghosh S, Dasgupta S (2010) Fibrillation in human serum albumin is enhanced in the presence of copper(II). J Phys Chem B 114(31):10228–10233PubMedGoogle Scholar
  109. Perrin RJ, Woods WS, Clayton DF, George JM (2000) Interaction of human alpha-synuclein and Parkinson’s disease variants with phospholipids. Structural analysis using site-directed mutagenesis. J Biol Chem 275(44):34393–34398PubMedGoogle Scholar
  110. Perrin RJ, Woods WS, Clayton DF, George JM (2001) Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins. J Biol Chem 276(45):41958–41962PubMedGoogle Scholar
  111. Pfefferkorn CM, Jiang Z, Lee JC (2012) Biophysics of alpha-synuclein membrane interactions. Biochim Biophys Acta 1818(2):162–171PubMedCentralPubMedGoogle Scholar
  112. Popovic M, De Biasio A, Pintar A, Pongor S (2007) The intracellular region of the Notch ligand Jagged-1 gains partial structure upon binding to synthetic membranes. FEBS J 274(20):5325–5336PubMedGoogle Scholar
  113. Prilusky J, Felder CE, Zeev-Ben-Mordehai T, Rydberg EH, Man O, Beckmann JS, Silman I, Sussman JL (2005) FoldIndex: a simple tool to predict whether a given protein sequence is intrinsically unfolded. Bioinformatics 21(16):3435–3438PubMedGoogle Scholar
  114. Ptitsyn OB, Bychkova VE, Uversky VN (1995) Kinetic and equilibrium folding intermediates. Philos Trans R Soc Lond B Biol Sci 348(1323):35–41PubMedGoogle Scholar
  115. Radivojac P, Iakoucheva LM, Oldfield CJ, Obradovic Z, Uversky VN, Dunker AK (2007) Intrinsic disorder and functional proteomics. Biophys J 92(5):1439–1456PubMedCentralPubMedGoogle Scholar
  116. Reiersen H, Rees AR (2000) Trifluoroethanol may form a solvent matrix for assisted hydrophobic interactions between peptide side chains. Protein Eng 13(11):739–743PubMedGoogle Scholar
  117. Rezaei-Ghaleh N, Amininasab M, Nemat-Gorgani M (2008) Conformational changes of alpha-chymotrypsin in a fibrillation-promoting condition: a molecular dynamics study. Biophys J 95(9):4139–4147PubMedCentralPubMedGoogle Scholar
  118. Rhoades E, Ramlall TF, Webb WW, Eliezer D (2006) Quantification of alpha-synuclein binding to lipid vesicles using fluorescence correlation spectroscopy. Biophys J 90(12):4692–4700PubMedCentralPubMedGoogle Scholar
  119. Roccatano D, Colombo G, Fioroni M, Mark AE (2002) Mechanism by which 2,2,2-trifluoroethanol/water mixtures stabilize secondary-structure formation in peptides: a molecular dynamics study. Proc Natl Acad Sci U S A 99(19):12179–12184PubMedCentralPubMedGoogle Scholar
  120. Rochet JC, Lansbury PT Jr (2000) Amyloid fibrillogenesis: themes and variations. Curr Opin Struct Biol 10(1):60–68PubMedGoogle Scholar
  121. Rodionova NA, Semisotnov GV, Kutyshenko VP, Uverskii VN, Bolotina IA (1989) Staged equilibrium of carbonic anhydrase unfolding in strong denaturants. Mol Biol 23(3):683–692Google Scholar
  122. Romero P, Obradovic Z, Li X, Garner EC, Brown CJ, Dunker AK (2001) Sequence complexity of disordered protein. Proteins 42(1):38–48PubMedGoogle Scholar
  123. Rozga M, Sokolowska M, Protas AM, Bal W (2007) Human serum albumin coordinates Cu(II) at its N-terminal binding site with 1 pM affinity. J Biol Inorg Chem 12(6):913–918PubMedGoogle Scholar
  124. Santambrogio C, Ricagno S, Sobott F, Colombo M, Bolognesi M, Grandori R (2011) Characterization of beta2-microglobulin conformational intermediates associated to different fibrillation conditions. J Mass Spectrom 46(8):734–741PubMedGoogle Scholar
  125. Semisotnov GV, Rodionova NA, Razgulyaev OI, Uversky VN, Gripas AF, Gilmanshin RI (1991) Study of the “molten globule” intermediate state in protein folding by a hydrophobic fluorescent probe. Biopolymers 31(1):119–128PubMedGoogle Scholar
  126. Shao H, Jao S, Ma K, Zagorski MG (1999) Solution structures of micelle-bound amyloid beta-(1–40) and beta-(1–42) peptides of Alzheimer’s disease. J Mol Biol 285(2):755–773PubMedGoogle Scholar
  127. Shirahama T, Cohen AS (1967) High-resolution electron microscopic analysis of the amyloid fibril. J Cell Biol 33(3):679–708PubMedCentralPubMedGoogle Scholar
  128. Shirahama T, Benson MD, Cohen AS, Tanaka A (1973) Fibrillar assemblage of variable segments of immunoglobulin light chains: an electron microscopic study. J Immunol 110(1):21–30PubMedGoogle Scholar
  129. Shvadchak VV, Falomir-Lockhart LJ, Yushchenko DA, Jovin TM (2011) Specificity and kinetics of alpha-synuclein binding to model membranes determined with fluorescent excited state intramolecular proton transfer (ESIPT) probe. J Biol Chem 286(15):13023–13032PubMedCentralPubMedGoogle Scholar
  130. Silva BA, Breydo L, Fink AL, Uversky VN (2013) Agrochemicals, alpha-synuclein, and Parkinson’s disease. Mol Neurobiol 47(2):598–612PubMedGoogle Scholar
  131. Sluzky V, Tamada JA, Klibanov AM, Langer R (1991) Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces. Proc Natl Acad Sci U S A 88(21):9377–9381PubMedCentralPubMedGoogle Scholar
  132. Smith DP, Jones S, Serpell LC, Sunde M, Radford SE (2003) A systematic investigation into the effect of protein destabilisation on beta 2-microglobulin amyloid formation. J Mol Biol 330(5):943–954PubMedGoogle Scholar
  133. Srisailam S, Kumar TK, Rajalingam D, Kathir KM, Sheu HS, Jan FJ, Chao PC, Yu C (2003) Amyloid-like fibril formation in an all beta-barrel protein. Partially structured intermediate state(s) is a precursor for fibril formation. J Biol Chem 278(20):17701–17709PubMedGoogle Scholar
  134. Sticht H, Bayer P, Willbold D, Dames S, Hilbich C, Beyreuther K, Frank RW, Rosch P (1995) Structure of amyloid A4-(1-40)-peptide of Alzheimer’s disease. Eur J Biochem 233(1):293–298PubMedGoogle Scholar
  135. Sunde M, Serpell LC, Bartlam M, Fraser PE, Pepys MB, Blake CC (1997) Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J Mol Biol 273(3):729–739PubMedGoogle Scholar
  136. Sung YH, Eliezer D (2006) Secondary structure and dynamics of micelle bound beta- and gamma-synuclein. Protein Sci 15(5):1162–1174PubMedCentralPubMedGoogle Scholar
  137. Sweede M, Ankem G, Chutvirasakul B, Azurmendi HF, Chbeir S, Watkins J, Helm RF, Finkielstein CV, Capelluto DG (2008) Structural and membrane binding properties of the prickle PET domain. Biochemistry 47(51):13524–13536PubMedGoogle Scholar
  138. Taboada P, Barbosa S, Castro E, Mosquera V (2006) Amyloid fibril formation and other aggregate species formed by human serum albumin association. J Phys Chem B 110(42):20733–20736PubMedGoogle Scholar
  139. Tamamizu-Kato S, Kosaraju MG, Kato H, Raussens V, Ruysschaert JM, Narayanaswami V (2006) Calcium-triggered membrane interaction of the alpha-synuclein acidic tail. Biochemistry 45(36):10947–10956PubMedGoogle Scholar
  140. Tanford C (1968) Protein denaturation. Adv Protein Chem 23:121–282PubMedGoogle Scholar
  141. Teplow DB (1998) Structural and kinetic features of amyloid beta-protein fibrillogenesis. Amyloid 5(2):121–142PubMedGoogle Scholar
  142. Thomas PD, Dill KA (1993) Local and nonlocal interactions in globular proteins and mechanisms of alcohol denaturation. Protein Sci 2(12):2050–2065PubMedCentralPubMedGoogle Scholar
  143. Tompa P (2002) Intrinsically unstructured proteins. Trends Biochem Sci 27(10):527–533PubMedGoogle Scholar
  144. Tompa P (2005) The interplay between structure and function in intrinsically unstructured proteins. FEBS Lett 579(15):3346–3354PubMedGoogle Scholar
  145. Tompa P, Csermely P (2004) The role of structural disorder in the function of RNA and protein chaperones. FASEB J 18(11):1169–1175PubMedGoogle Scholar
  146. Ulmer TS, Bax A (2005) Comparison of structure and dynamics of micelle-bound human alpha-synuclein and Parkinson disease variants. J Biol Chem 280(52):43179–43187PubMedGoogle Scholar
  147. Ulmer TS, Bax A, Cole NB, Nussbaum RL (2005) Structure and dynamics of micelle-bound human alpha-synuclein. J Biol Chem 280(10):9595–9603PubMedGoogle Scholar
  148. Uversky VN (2003a) A protein-chameleon: conformational plasticity of alpha-synuclein, a disordered protein involved in neurodegenerative disorders. J Biomol Struct Dyn 21(2):211–234PubMedGoogle Scholar
  149. Uversky VN (2003b) Protein folding revisited. A polypeptide chain at the folding-misfolding-nonfolding cross-roads: which way to go? Cell Mol Life Sci 60(9):1852–1871PubMedGoogle Scholar
  150. Uversky VN (2004) Neurotoxicant-induced animal models of Parkinson’s disease: understanding the role of rotenone, maneb and paraquat in neurodegeneration. Cell Tissue Res 318(1):225–241PubMedGoogle Scholar
  151. Uversky VN (2007) Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation. J Neurochem 103(1):17–37PubMedGoogle Scholar
  152. Uversky VN (2008a) Alpha-synuclein misfolding and neurodegenerative diseases. Curr Protein Pept Sci 9(5):507–540PubMedGoogle Scholar
  153. Uversky VN (2008b) Amyloidogenesis of natively unfolded proteins. Curr Alzheimer Res 5(3):260–287PubMedCentralPubMedGoogle Scholar
  154. Uversky VN (2009a) Intrinsic disorder in proteins associated with neurodegenerative diseases. Front Biosci 14:5188–5238Google Scholar
  155. Uversky VN (2009b) Intrinsically disordered proteins and their environment: effects of strong denaturants, temperature, pH, counter ions, membranes, binding partners, osmolytes, and macromolecular crowding. Protein J 28(7–8):305–325PubMedGoogle Scholar
  156. Uversky VN (2011a) Intrinsically disordered proteins from A to Z. Int J Biochem Cell Biol 43(8):1090–1103PubMedGoogle Scholar
  157. Uversky VN (2011b) Multitude of binding modes attainable by intrinsically disordered proteins: a portrait gallery of disorder-based complexes. Chem Soc Rev 40(3):1623–1634PubMedGoogle Scholar
  158. Uversky VN (2013a) A decade and a half of protein intrinsic disorder: biology still waits for physics. Protein Sci 22(6):693–724PubMedCentralPubMedGoogle Scholar
  159. Uversky VN (2013b) Intrinsic disorder-based protein interactions and their modulators. Curr Pharm Des 19(23):4191–4213PubMedGoogle Scholar
  160. Uversky VN (2013c) Unusual biophysics of intrinsically disordered proteins. Biochim Biophys Acta 1834(5):932–951PubMedGoogle Scholar
  161. Uversky VN, Eliezer D (2009) Biophysics of Parkinson’s disease: structure and aggregation of alpha-synuclein. Curr Protein Pept Sci 10(5):483–499PubMedCentralPubMedGoogle Scholar
  162. Uversky VN, Fink AL (2004) Conformational constraints for amyloid fibrillation: the importance of being unfolded. Biochim Biophys Acta 1698(2):131–153PubMedGoogle Scholar
  163. Uversky VN, Narizhneva NV, Kirschstein SO, Winter S, Lober G (1997) Conformational transitions provoked by organic solvents in beta-lactoglobulin: can a molten globule like intermediate be induced by the decrease in dielectric constant? Fold Des 2(3):163–172PubMedGoogle Scholar
  164. Uversky VN, Talapatra A, Gillespie JR, Fink AL (1999a) Protein deposits as the molecular basis of amyloidosis. I. Systemic amyloidosis. Med Sci Monit 5:1001–1012Google Scholar
  165. Uversky VN, Talapatra A, Gillespie JR, Fink AL (1999b) Protein deposits as the molecular basis of amyloidosis. II. Localized amyloidosis and neurodegenerative disorders. Med Sci Monit 5:1238–1254Google Scholar
  166. Uversky VN, Gillespie JR, Fink AL (2000) Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins 41(3):415–427PubMedGoogle Scholar
  167. Uversky VN, Li J, Fink AL (2001a) Evidence for a partially folded intermediate in alpha-synuclein fibril formation. J Biol Chem 276(14):10737–10744PubMedGoogle Scholar
  168. Uversky VN, Li J, Fink AL (2001b) Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular link between Parkinson’s disease and heavy metal exposure. J Biol Chem 276(47):44284–44296PubMedGoogle Scholar
  169. Uversky VN, Li J, Fink AL (2001c) Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a possible factor in Parkinson’s disease. FEBS Lett 500(3):105–108PubMedGoogle Scholar
  170. Uversky VN, Li J, Fink AL (2001d) Trimethylamine-N-oxide-induced folding of alpha-synuclein. FEBS Lett 509(1):31–35PubMedGoogle Scholar
  171. Uversky VN, Li J, Bower K, Fink AL (2002a) Synergistic effects of pesticides and metals on the fibrillation of alpha-synuclein: implications for Parkinson’s disease. Neurotoxicology 23(4–5):527–536PubMedGoogle Scholar
  172. Uversky VN, Li J, Souillac P, Millett IS, Doniach S, Jakes R, Goedert M, Fink AL (2002b) Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins. J Biol Chem 277(14):11970–11978PubMedGoogle Scholar
  173. Uversky VN, Oldfield CJ, Dunker AK (2005) Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling. J Mol Recognit 18(5):343–384PubMedGoogle Scholar
  174. van Rooijen BD, Claessens MM, Subramaniam V (2008) Membrane binding of oligomeric alpha-synuclein depends on bilayer charge and packing. FEBS Lett 582(27):3788–3792PubMedGoogle Scholar
  175. van Rooijen BD, Claessens MM, Subramaniam V (2009) Lipid bilayer disruption by oligomeric alpha-synuclein depends on bilayer charge and accessibility of the hydrophobic core. Biochim Biophys Acta 1788(6):1271–1278PubMedGoogle Scholar
  176. Volles MJ, Lee SJ, Rochet JC, Shtilerman MD, Ding TT, Kessler JC, Lansbury PT Jr (2001) Vesicle permeabilization by protofibrillar alpha-synuclein: implications for the pathogenesis and treatment of Parkinson’s disease. Biochemistry 40(26):7812–7819PubMedGoogle Scholar
  177. Vucetic S, Xie H, Iakoucheva LM, Oldfield CJ, Dunker AK, Obradovic Z, Uversky VN (2007) Functional anthology of intrinsic disorder 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions. J Proteome Res 6(5):1899–1916PubMedCentralPubMedGoogle Scholar
  178. Walgers R, Lee TC, Cammers-Goodwin A (1998) An indirect chaotropic mechanism of the stabilization of helix conformation of peptides in aqueous trifluoroethanol and hexafluoro-2-propanol. J Am Chem Soc 120:5073–5079Google Scholar
  179. Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB (1997) Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate. J Biol Chem 272(35):22364–22372PubMedGoogle Scholar
  180. Walsh DM, Hartley DM, Kusumoto Y, Fezoui Y, Condron MM, Lomakin A, Benedek GB, Selkoe DJ, Teplow DB (1999) Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J Biol Chem 274(36):25945–25952PubMedGoogle Scholar
  181. Ward JJ, McGuffin LJ, Bryson K, Buxton BF, Jones DT (2004a) The DISOPRED server for the prediction of protein disorder. Bioinformatics 20(13):2138–2139PubMedGoogle Scholar
  182. Ward JJ, Sodhi JS, McGuffin LJ, Buxton BF, Jones DT (2004b) Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J Mol Biol 337(3):635–645PubMedGoogle Scholar
  183. Weinreb PH, Zhen W, Poon AW, Conway KA, Lansbury PT Jr (1996) NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry 35(43):13709–13715PubMedGoogle Scholar
  184. Wilkinson KD, Mayer AN (1986) Alcohol-induced conformational changes of ubiquitin. Arch Biochem Biophys 250(2):390–399PubMedGoogle Scholar
  185. Williams RM, Obradovi Z, Mathura V, Braun W, Garner EC, Young J, Takayama S, Brown CJ, Dunker AK (2001) The protein non-folding problem: amino acid determinants of intrinsic order and disorder. Pac Symp Biocomput 89–100Google Scholar
  186. Wright HT (1973) Comparison of the crystal structures of chymotrypsinogen-A and alpha-chymotrypsin. J Mol Biol 79(1):1–11PubMedGoogle Scholar
  187. Wright PE, Dyson HJ (1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J Mol Biol 293(2):321–331PubMedGoogle Scholar
  188. Wu KP, Baum J (2010) Detection of transient interchain interactions in the intrinsically disordered protein alpha-synuclein by NMR paramagnetic relaxation enhancement. J Am Chem Soc 132(16):5546–5547PubMedCentralPubMedGoogle Scholar
  189. Wu KP, Kim S, Fela DA, Baum J (2008) Characterization of conformational and dynamic properties of natively unfolded human and mouse alpha-synuclein ensembles by NMR: implication for aggregation. J Mol Biol 378(5):1104–1115PubMedCentralPubMedGoogle Scholar
  190. Xie H, Vucetic S, Iakoucheva LM, Oldfield CJ, Dunker AK, Obradovic Z, Uversky VN (2007a) Functional anthology of intrinsic disorder 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins. J Proteome Res 6(5):1917–1932PubMedCentralPubMedGoogle Scholar
  191. Xie H, Vucetic S, Iakoucheva LM, Oldfield CJ, Dunker AK, Uversky VN, Obradovic Z (2007b) Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J Proteome Res 6(5):1882–1898PubMedCentralPubMedGoogle Scholar
  192. Yamaguchi K, Naiki H, Goto Y (2006) Mechanism by which the amyloid-like fibrils of a beta 2-microglobulin fragment are induced by fluorine-substituted alcohols. J Mol Biol 363(1):279–288PubMedGoogle Scholar
  193. Zerovnik E (2002) Amyloid-fibril formation. Proposed mechanisms and relevance to conformational disease. Eur J Biochem 269(14):3362–3371PubMedGoogle Scholar
  194. Zhu M, Fink AL (2003) Lipid binding inhibits alpha-synuclein fibril formation. J Biol Chem 278(19):16873–16877PubMedGoogle Scholar
  195. Zhu M, Li J, Fink AL (2003) The association of alpha-synuclein with membranes affects bilayer structure, stability, and fibril formation. J Biol Chem 278(41):40186–40197PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of MedicineUniversity of South FloridaTampaUSA
  2. 2.Biology Department, Faculty of ScienceKing Abdulaziz UniversityJeddahKingdom of Saudi Arabia
  3. 3.Institute for Biological InstrumentationRussian Academy of SciencesPushchinoRussia
  4. 4.Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia

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