Alpha-synuclein and familial variants affect the chain order and the thermotropic phase behavior of anionic lipid vesicles

Biochimica et Biophysica Acta - Proteins and Proteomics

Volumn 1864, Issue 9, 2016, Pages 1206-1214

  Pantusa, Manuela ^a   Vad, Brian ^b   Lillelund, Ove ^b   Kjær, Lars ^b   Otzen, Daniel ^b   Bartucci, Rosa ^a  

^a UNIVERSITY OF CALABRIA   (Italy)

^b AARHUS UNIVERSITY   (Denmark)

Author keywords

Alpha synuclein; CD; Coil helix transition; DSC; Lipid bilayers; Spinlabel ESR

Indexed keywords

ALPHA SYNUCLEIN; DIMYRISTOYLPHOSPHATIDYLGLYCEROL; LIPID BILAYER; PHOSPHATIDYLCHOLINE; PHOSPHATIDYLGLYCEROL; PROTEIN BINDING; RECOMBINANT PROTEIN; SOLUTION AND SOLUBILITY;

ARTICLE; CALORIMETRY; CIRCULAR DICHROISM; ELECTRON SPIN RESONANCE; LIPID BILAYER; LIPID VESICLE; PRIORITY JOURNAL; PROTEIN LIPID INTERACTION; STOICHIOMETRY; TEMPERATURE; WILD TYPE; ALPHA HELIX; AMINO ACID SUBSTITUTION; BETA SHEET; CHEMISTRY; GENE EXPRESSION; GENETICS; HUMAN; MUTATION; PHASE TRANSITION; PROTEIN DOMAIN; PROTEIN FOLDING; SOLUTION AND SOLUBILITY; STRUCTURE ACTIVITY RELATION; THERMODYNAMICS;

ALPHA-SYNUCLEIN; AMINO ACID SUBSTITUTION; GENE EXPRESSION; HUMANS; LIPID BILAYERS; MUTATION; PHASE TRANSITION; PHOSPHATIDYLCHOLINES; PHOSPHATIDYLGLYCEROLS; PROTEIN BINDING; PROTEIN CONFORMATION, ALPHA-HELICAL; PROTEIN CONFORMATION, BETA-STRAND; PROTEIN FOLDING; PROTEIN INTERACTION DOMAINS AND MOTIFS; RECOMBINANT PROTEINS; SOLUTIONS; STRUCTURE-ACTIVITY RELATIONSHIP; THERMODYNAMICS;

EID: 84969724121     PISSN: 15709639     EISSN: 18781454     Source Type: Journal    
DOI: 10.1016/j.bbapap.2016.05.003     Document Type: Article

References (72)

1. [1] Fauvet, B., Mbefo, M.K.… Lashuel, H.A., α-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. J. Biol. Chem. 287 (2012), 15345–15364.
2. [2] McLean, P.J., Kawamata, H.… Hyman, B.T., Membrane association and protein conformation of alpha-synuclein in intact neurons. Effect of Parkinson's disease-linked mutations. J. Biol. Chem. 275 (2000), 8812–8816.
3. [3] Davidson, W.S., Jonas, A.… George, J.M., Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J. Biol. Chem. 273 (1998), 9443–9449.
4. [4] Jo, E., McLaurin, J.… Fraser, P.E., Alpha-synuclein membrane interactions and lipid specificity. J. Biol. Chem. 275 (2000), 34328–34334.
5. [5] Perrin, R.J., Woods, W.S.… George, J.M., Interaction of human α-synuclein and Parkinson's disease variants with phospholipids. Structural analysis using site-directed mutagenesis. J. Biol. Chem. 275 (2000), 34393–34398.
6. [6] Eliezer, D., Kutluay, E.… Browne, G., Conformational properties of α-synuclein in its free and lipid associated states. J. Mol. Biol. 307 (2001), 1061–1073.
7. [7] Nuscher, B., Kamp, F.… Beyer, K., α-Synuclein has a high affinity for packing defects in a bilayer membrane. J. Biol. Chem. 229 (2004), 21966–21975.
8. [8] Conway, K.A., Harper, J.D., Lansbury, P.T. Jr., Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson's disease are typical amyloid. Biochemistry 39 (2000), 2552–2563.
9. [9] Conway, K.A., Lee, S.J.… Lansbury, P.T., Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: Implications for pathogenesis and therapy. Proc. Natl. Acad. Sci. U. S. A. 97 (2000), 571–576.
10. [10] Fink, A.L., The aggregation and fibrillation of alpha-synuclein. Acc. Chem. Res. 39 (2006), 628–634.
11. [11] Uversky, V.N., Eliezer, D., Biophysics of Parkinson's disease: structure and aggregation of alpha-synuclein. Curr. Protein Pept. Sci. 10 (2009), 483–499.
12. [12] Giehm, L., Lorenzen, N., Otzen, D.E., Assays for α-synuclein aggregation. Methods 53 (2011), 295–305.
13. [13] Giehm, L., Svergun, D.I.… Vestergaard, B., Low-resolution structure of a vesicle disrupting alpha-synuclein oligomer that accumulates during fibrillation. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 3246–3251.
14. [14] Lorenzen, N., Nielsen, S.B.… Otzen, D.E., The role of stable α-synuclein oligomers in the molecular events underlying amyloid formation. J. Am. Chem. Soc. 136 (2014), 3859–3868.
15. [15] Paslawski, W., Mysling, S.… Otzen, D.E., Co-existence of two different α-synuclein oligomers with different core structures determined by hydrogen/deuterium exchange mass spectrometry. Angew. Chem. Int. Ed. Engl. 53 (2014), 7560–7563.
16. [16] Duda, J.E., Lee, V.M.Y., Trojanowski, J.Q., Neuropathology of synuclein aggregates: new insights into mechanisms of neurodegenerative diseases. J. Neurosci. Res. 61 (2000), 121–127.
17. [17] Chartier-Harlin, M.C., Kachergus, J.… Destée, A., α-synuclein locus duplication in a case of familial Parkinson's disease. Lancet 364 (2004), 1167–1169.
18. [18] Singleton, A.B., Farrer, M.… Gwinn-Hardy, K., α-Synuclein locus triplication causes Parkinson's disease. Science, 302, 2003, 84.
19. [19] Polymeropoulos, M.H., Lavedan, C.… Nussbaum, R.I., Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276 (1997), 2045–2047.
20. [20] Kruger, R., Kuhn, W.… Riess, O., Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease. Nat. Genet. 18 (1998), 106–108.
21. [21] Zarranz, J.J., Alegre, J.… Yebenes, d.J.G., The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55 (2004), 164–173.
22. [22] Appel-Cresswell, S., Vilarino-Guell, C.… Farrer, M.J., Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease. Mov. Disord. 28 (2013), 811–813.
23. [23] Proukakis, C., Dudzik, C.G.… Schapira, A.H., A novel α-synuclein missense mutation in Parkinson's disease. Neurology 80 (2013), 1062–1064.
24. [24] Kiely, A.P., Asi, Y.T.… Holton, J.L., α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy?. Acta Neuropathol. 125 (2013), 753–769.
25. [25] Lesage, S., Anheim, M.… Brice, A., G51D, α-synuclein mutation causes a novel Parkinsonian–pyramidal syndrome. Ann. Neurol. 73 (2013), 459–471.
26. [26] Pasanen, P., Myllykangas, L.… Paetau, A., A novel alpha-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology. Neurobiol. Aging 35 (2014), 2180.e1–2180.e5.
27. [27] Segrest, J.P., Jones, M.K.… Anantharamaiah, G.M., The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function. J. Lipid Res. 33 (1992), 141–166.
28. [28] Chandra, S., Chen, X.… Sudhof, T.C., A broken α-helix in folded α-synuclein. J. Biol. Chem. 278 (2003), 15313–15318.
29. [29] Kamp, F., Beyer, K., Binding of α-synuclein affects the lipid packing in bilayers of small vesicles. J. Biol. Chem. 28 (2006), 9251–9259.
30. [30] Stöckl, M., Fischer, P.… Herrmann, A., Alpha-synuclein selectively binds to anionic phospholipids embedded in liquid-disordered domains. J. Mol. Biol. 375 (2008), 1394–1404.
31. [31] Kjaer, L., Giehm, L.… Otzen, D.E., The influence of vesicle size and composition on alpha-synuclein structure and stability. Biophys. J. 96 (2009), 2857–2870.
32. [32] Wietek, J., Haralampiev, I.… Stockl, M., Membrane bound a-synuclein is fully embedded in the lipid bilayer while segments with higher flexibility remain. FEBS Lett. 587 (2013), 2572–2577.
33. [33] Lorenzen, N., Lemminger, L.… Otzen, D.E., The N-terminus of α-synuclein is essential for both monomeric and oligomeric interactions with membranes. FEBS Lett. 588 (2014), 497–502.
34. [34] Bartels, T., Ahlstrom, L.S.… Beyer, K., The N-terminus of the intrinsically disordered protein alpha-synuclein triggers membrane binding and helix folding. Biophys. J. 99 (2010), 2116–2124.
35. [35] Murphy, D.D., Rueter, S.M.… Lee, V.M., Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J. Neurosci. 20 (2000), 3214–3220.
36. [36] Cabin, D.E., Shimazu, K.… Nussbaum, R.L., Synaptic vesicles depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J. Neurosci. 22 (2002), 8787–8807.
37. [37] Beyer, K., Mechanistic aspects of Parkinson's disease: alpha-synuclein and the biomembrane. Cell Biochem. Biophys. 47 (2007), 285–299.
38. [38] Volles, M.J., Lee, S.J.… Lansbury, P.T. Jr., Vesicle permeabilization by protofibrillar alpha-synuclein: implications for the pathogenesis and treatment of Parkinson's disease. Biochemistry 40 (2001), 7812–7819.
39. [39] Kayed, R., Sokolov, Y.… Glabe, C.G., Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein misfolding diseases. J. Biol. Chem. 279 (2004), 46363–46366.
40. [40] Galvagnion, C., Buell, A.K.… Dobson, C.M., Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation. Nat. Chem. Biol. 11 (2015), 229–234.
41. [41] Ramakrishnan, M., Jensen, P.H., Marsh, D., α-Synuclein association with phosphatidylglycerol probed by lipid spin labels. Biochemistry 42 (2003), 12919–12926.
42. [42] Jao, C., der-Sarkissian, A.… Langen, R., Structure of membrane-bound α-synuclein studied by site-directed spin labeling. Proc. Natl. Acad. Sci. U. S. A. 101 (2004), 8331–8336.
43. [43] Bisaglia, M., Tessari, I.… Mammì, S., A topological model of the interaction between alpha-synuclein and sodium dodecyl sulfate micelles. Biochemistry 44 (2005), 329–339.
44. [44] Bussell, R. Jr., Ramlall, T.F., Eliezer, D., Helix periodicity, topology, and dynamics of membrane-associated alpha-synuclein. Protein Sci. 14 (2005), 862–872.
45. [45] Ramakrishnan, M., Jensen, P.H., Marsh, D., Association of α-synuclein and mutants with lipid membranes: spin-label ESR and polarized IR. Biochemistry 45 (2006), 3386–3395.
46. [46] Georgieva, E.R., Ramlall, T.F.… Eliezer, D., Membrane-bound alpha-synuclein forms an extended helix: long-distance pulsed ESR measurements using vesicles, bicelles, and rodlike micelles. J. Am. Chem. Soc. 130 (2008), 12856–12857.
47. [47] Jao, C.C., Hegde, B.G.… Langen, R., Structure of membrane-bound alpha-synuclein from site-directed spin labeling and computational refinement. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 19666–19671.
48. [48] Pelmutter, J.D., Braun, A.R., Sachs, J.N., Curvature dynamics of alpha-synuclein familial Parkinson disease mutants: molecular simulations of the micelle- and bilayer-bound forms. J. Biol. Chem. 284 (2009), 7177–7189.
49. [49] Georgieva, E.R., Ramlall, T.F.… Eliezer, D., The lipid-binding domain of wild type and mutant alpha-synuclein: compactness and interconversion between the broken and extended helix forms. J. Biol. Chem. 285 (2010), 28261–28274.
50. [50] Grey, M., Linse, S.… Sparr, E., Membrane interaction of alpha-synuclein in different aggregation states. J. Park. Dis. 1 (2011), 359–371.
51. [51] Pfefferkorn, C.M., Heinrich, F.… Lee, J.C., Depth of a-synuclein in a bilayer determined by fluorescence, neutron reflectometry, and computation. Biophys. J. 102 (2012), 613–621.
52. 13C NMR reveals annealing of raft-like membranes containing cholesterol by intrinsically disordered protein α-synuclein. J. Mol. Biol. 425 (2013), 2973–2987.
53. [53] Ouberai, M.M., Wang, J.… Welland, M.E., Alpha-synuclein senses lipid packing defects and induces lateral expansion of lipids leading to membrane remodeling. J. Biol. Chem. 288 (2013), 20883–20895.
54. [54] Stockl, M.T., Zijlstra, N., Subramaniam, V., Alpha-synuclein oligomers: an amyloid pore? Insights into mechanisms of alpha-synuclein oligomer–lipid interactions. Mol. Neurobiol. 47 (2013), 613–621.
55. [55] Westphal, C.H., Chandra, S.S., Monomeric synucleins generate membrane curvature. J. Biol. Chem. 288 (2013), 1829–1840.
56. [56] Marsh, D., Electron Spin Resonance: Spin-Labels. Grell, E., (eds.) Membrane Spectroscopy: Molecular Biology Biochemistry and Biophysics, Vol. 31, 1981, Springer, Berlin, 51–142.
57. [57] Marsh, D., Electron spin resonance in membrane research: protein-lipid interactions. Methods 46 (2008), 83–96.
58. [58] Vad, B.S., Balakrishnan, V.S.… Otzen, D.E., Phospholipid ether linkages significantly modulate the membrane affinity of the antimicrobial peptide novicidin. J. Mem. Biol. 248 (2015), 487–496.
59. [59] Zhang, Y.P., Lewis, R.N., McElhaney, R.N., Calorimetric and spectroscopic studies of the thermotropic phase behavior of the n-saturated 1.2-diacylphosphatidylglycerols. Biophys. J. 72 (1997), 779–793.
60. [60] Riske, K.A., Dobereiner, H.-G., Lamy-Freund, M.T., Gel–fluid transition in dilute versus concentrated DMPG aqueous dispersions. J. Phys. Chem. B 106 (2002), 239–246.
61. [61] Chiu, M.H., Prenner, E.J., Differential scanning calorimetry: an invaluable tool for a detailed thermodynamic characterization of macromolecules and their interactions. J. Pharm. Bioallied Sci. 3 (2011), 39–59.
62. [62] Bodner, C.R., Maltsev, A.S.… Bax, A., Differential phospholipid binding of alpha-synuclein variants implicated in Parkinson's disease revealed by solution NMR spectroscopy. Biochemistry 49 (2010), 862–871.
63. [63] Jensen, P.H., Nielsen, M.S.… Goedert, M., Binding of α-synuclein to brain vesicles is abolished by familial Parkinson's disease mutation. J. Biol. Chem. 273 (1998), 26292–26294.
64. [64] Choi, W., Zibaee, S.… Goedert, M., Mutation E46K increases phospholipid binding and assembly into filaments of human α-synuclein. FEBS Letters. 576 (2004), 363–368.
65. [65] White, S.H., Wimley, W.C., Membrane protein folding and stability: physical principles. Annu. Rev. Biophys. Biomol. Struct. 28 (1999), 319–365.
66. [66] Sahay, S., Ghosh, D.… Maji, S.K., Familial Parkinson's disease associated mutations alter the site-specific microenvironment and dynamics of alpha-synuclein. J. Biol. Chem. 290 (2015), 7804–7822.
67. [67] Mbefo, M., Fares, M.B.… Lashuel, H.A., The Parkinson's disease mutant E46K enhances alpha-synuclein phosphorylation in mammalian cell-lines, in yeast and in vivo. J. Biol. Chem. 290 (2015), 9412–9427.
68. [68] Li, J., Uversky, V.N., Fink, A.L., Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein. Biochemistry 40 (2001), 11604–11613.
69. [69] Moussa, C.E., Wersinger, C.… Sidhu, A., Differential cytotoxicity of human wild type and mutant alpha-synuclein in human neuroblastoma SH-SY5Y cells in the presence of dopamine. Biochemistry 43 (2004), 5539–5550.
70. [70] Stefanis, L., Larsen, K.E.… Greene, L.A., Expression of A53T mutant but not wild-type alpha-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. J. Neurosci. 21 (2001), 9549–9560.
71. [71] Greenbaum, E.A., Graves, C.L.… Giasson, B.I., The E46K mutation in alpha-synuclein increases amyloid fibril formation. J. Biol. Chem. 280 (2005), 7800–7807.
72. [72] Diao, J., Burré, J.… Brunger, A.T., wt alpha-synuclein induces clustering of synaptic-vesicle mimics via binding to phospholipids and synaptobrevin 2/VAMP2. Elife, 2, 2013, e00592.