N-terminal Acetylation stabilizes N-terminal Helicity in Lipid- and Micelle-bound α-Synuclein and increases its affinity for Physiological Membranes

Journal of Biological Chemistry

Volumn 289, Issue 6, 2014, Pages 3652-3665

  Dikiy, Igor ^a   Eliezer, David ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LIPID-BINDING PROTEIN; N-TERMINAL ACETYLATION; PARKINSON DISEASE; POST TRANSLATIONAL MODIFICATION; PROTEIN AGGREGATION; SYNUCLEIN; Α-SYNUCLEIN;

ACETYLATION; ALPHA-SYNUCLEIN; GLUCOSIDES; HUMANS; MEMBRANES, ARTIFICIAL; MICELLES; MODELS, MOLECULAR; PROTEIN STABILITY; PROTEIN STRUCTURE, SECONDARY; SODIUM DODECYL SULFATE;

EID: 84893667535     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.512459     Document Type: Article

References (84)

1. Arnesen, T., Van Damme, P., Polevoda, B., Helsens, K., Evjenth, R., Colaert, N., Varhaug, J. E., Vandekerckhove, J., Lillehaug, J. R., Sherman, F., and Gevaert, K. (2009) Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans. Proc. Natl. Acad. Sci. U.S.A. 106, 8157-8162
2. Hwang, C.-S., Shemorry, A., and Varshavsky, A. (2010) N-terminal acetylation of cellular proteins creates specific degradation signals. Science 327, 973-977
3. Jarvis, J. A., Ryan, M. T., Hoogenraad, N. J., Craik, D. J., and Høj, P. B. (1995) Solution structure of the acetylated and noncleavable mitochondrial targeting signal of rat chaperonin 10. J. Biol. Chem. 270, 1323-1331
4. Kimura, Y., Takaoka, M., Tanaka, S., Sassa, H., Tanaka, K., Polevoda, B., Sherman, F., and Hirano, H. (2000) n-Acetylation and proteolytic activity of the yeast 20 S proteasome. J. Biol. Chem. 275, 4635-4639
5. Scott, D. C., Monda, J. K., Bennett, E. J., Harper, J. W., and Schulman, B. A. (2011) N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex. Science 334, 674-678
6. Shemorry, A., Hwang, C.-S., and Varshavsky, A. (2013) Control of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway. Mol. Cell 50, 540-551
7. Skoumpla, K., Coulton, A. T., Lehman, W., Geeves, M. A., and Mulvihill, D. P. (2007) Acetylation regulates tropomyosin function in the fission yeast Schizosaccharomyces pombe. J. Cell Sci. 120, 1635-1645
8. Devine, M. J., Gwinn, K., Singleton, A., and Hardy, J. (2011) Parkinson's disease and-synuclein expression. Mov. Disord. 26, 2160-2168
9. Stefanis, L. (2012)-Synuclein in Parkinson's disease. Cold Spring Harb. Perspect. Biol. 2, 10.1101/cshperspect.a009399
10. Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., and Goedert, M. (1998)-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc. Natl. Acad. Sci. U.S.A. 95, 6469-6473
11. Kiely, A. P., Asi, Y. T., Kara, E., Limousin, P., Ling, H., Lewis, P., Proukakis, C., Quinn, N., Lees, A. J., Hardy, J., Revesz, T., Houlden, H., and Holton, J. L. (2013)-Synucleinopathy associated with G51D SNCA mutation. A link between Parkinson's disease and multiple system atrophy? Acta Neuropathol. 125, 753-769
12. Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schöls, L., and Riess, O. (1998) Ala30Pro mutation in the gene encoding-synuclein in Parkinson's disease. Nat. Genet. 18, 106-108
13. Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E. S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W. G., Lazzarini, A. M., Duvoisin, R. C., Di Iorio, G., Golbe, L. I., and Nussbaum, R. L. (1997) Mutation in the-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047
14. Proukakis, C., Dudzik, C. G., Brier, T., MacKay, D. S., Cooper, J. M., Millhauser, G. L., Houlden, H., and Schapira, A. H. (2013) A novel-synuclein missense mutation in Parkinson disease. Neurology 80, 1062-1064
15. Zarranz, J. J., Alegre, J., Gómez-Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atarés, B., Llorens, V., Gomez Tortosa, E., del Ser, T.,Muñoz, D. G., and de Yebenes, J. G. (2004) The new mutation, E46K, of-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55, 164-173
16. Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W. H., Castillo, P. E., Shinsky, N., Verdugo, J. M., Armanini, M., Ryan, A., Hynes, M., Phillips, H., Sulzer, D., and Rosenthal, A. (2000) Mice lacking-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25, 239-252
17. Cabin, D. E., Shimazu, K., Murphy, D., Cole, N. B., Gottschalk, W., McIlwain, K. L., Orrison, B., Chen, A., Ellis, C. E., Paylor, R., Lu, B., and Nussbaum, R. L. (2002) Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking-synuclein. J. Neurosci. 22, 8797-8807
18. Chandra, S., Gallardo, G., Fernández-Chacón, R., Schlüter, O. M., and Südhof, T. C. (2005)-Synuclein cooperates with CSP-in preventing neurodegeneration. Cell 123, 383-396
19. Chandra, S., Fornai, F., Kwon, H.-B., Yazdani, U., Atasoy, D., Liu, X., Hammer, R. E., Battaglia, G., German, D. C., Castillo, P. E., and Südhof, T. C. (2004) Double-knockout mice for-And-synucleins. Effect on synaptic functions. Proc. Natl. Acad. Sci. U.S.A. 101, 14966-14971
20. Cooper, A. A., Gitler, A. D., Cashikar, A., Haynes, C. M., Hill, K. J., Bhullar, B., Liu, K., Xu, K., Strathearn, K. E., Liu, F., Cao, S., Caldwell, K. A., Caldwell, G. A., Marsischky, G., Kolodner, R. D., Labaer, J., Rochet, J.-C., Bonini, N. M., and Lindquist, S. (2006)-Synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313, 324-328
21. Liu, S., Ninan, I., Antonova, I., Battaglia, F., Trinchese, F., Narasanna, A., Kolodilov, N., Dauer, W., Hawkins, R. D., and Arancio, O. (2004)-Synuclein produces a long-lasting increase in neurotransmitter release. EMBO J. 23, 4506-4516
22. Murphy, D. D., Rueter, S. M., Trojanowski, J. Q., and Lee, V. M. (2000) Synucleins are developmentally expressed, and-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J. Neurosci. 20, 3214-3220
23. Nemani, V. M., Lu, W., Berge, V., Nakamura, K., Onoa, B., Lee, M. K., Chaudhry, F. A., Nicoll, R. A., and Edwards, R. H. (2010) Increased expression of-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65, 66-79
24. Bartels, T., Choi, J. G., and Selkoe, D. (2011)-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477, 107-110
25. Trexler, A. J., and Rhoades, E. (2012) N-terminal acetylation is critical for forming-helical oligomer of-synuclein. Protein Sci. 21, 601-605
26. Wang, W., Perovic, I., Chittuluru, J., Kaganovich, A., Nguyen, L. T., Liao, J., Auclair, J. R., Johnson, D., Landeru, A., Simorellis, A. K., Ju, S., Cookson, M. R., Asturias, F. J., Agar, J. N., Webb, B. N., Kang, C., Ringe, D., Petsko, G. A., Pochapsky, T. C., and Hoang, Q. Q. (2011) A soluble-synuclein construct forms a dynamic tetramer. Proc. Natl. Acad. Sci. U.S.A. 108, 17797-17802
27. Anderson, J. P., Walker, D. E., Goldstein, J. M., de Laat, R., Banducci, K., Caccavello, R. J., Barbour, R., Huang, J., Kling, K., Lee, M., Diep, L., Keim, P. S., Shen, X., Chataway, T., Schlossmacher, M. G., Seubert, P., Schenk, D., Sinha, S., Gai, W. P., and Chilcote, T. J. (2006) Phosphorylation of Ser-129 is the dominant pathological modification of-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem. 281, 29739-29752
28. Binolfi, A., Theillet, F.-X., and Selenko, P. (2012) Bacterial in-cell NMR of human-synuclein. A disordered monomer by nature? Biochem. Soc. Trans. 40, 950-954
29. Burré, J., Vivona, S., Diao, J., Sharma, M., Brunger, A. T., and Südhof, T. C. (2013) Properties of native brain-synuclein. Nature 498, E4-E6; discussion E6-E7
30. Fauvet, B., Fares, M.-B., Samuel, F., Dikiy, I., Tandon, A., Eliezer, D., and Lashuel, H. A. (2012) Characterization of semisynthetic and naturallyN-Acetylated-synuclein in vitro and in intact cells. Implications for aggregation and cellular properties of-synuclein. J. Biol. Chem. 287, 28243-28262
31. Fauvet, B., Mbefo, M. K., Fares, M.-B., Desobry, C., Michael, S., Ardah, M. T., Tsika, E., Coune, P., Prudent, M., Lion, N., Eliezer, D., Moore, D. J., Schneider, B., Aebischer, P., El-Agnaf, O. M., Masliah, E., and Lashuel, H. A. (2012)-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. J. Biol. Chem. 287, 15345-15364
32. Kang, L., Moriarty, G. M., Woods, L. A., Ashcroft, A. E., Radford, S. E., and Baum, J. (2012) N-terminal acetylation of-synuclein induces increased transient helical propensity and decreased aggregation rates in the intrinsically disordered monomer. Protein Sci. 21, 911-917
33. Maltsev, A. S., Ying, J., and Bax, A. (2012) Impact of N-terminal acetylation of-synuclein on its random coil and lipid binding properties. Biochemistry 51, 5004-5013
34. Davidson, W. S., Jonas, A., Clayton, D. F., and George, J. M. (1998) Stabilization of-synuclein secondary structure upon binding to synthetic membranes. J. Biol. Chem. 273, 9443-9449
35. Eliezer, D., Kutluay, E., Bussell, R., Jr., and Browne, G. (2001) Conformational properties of-synuclein in its free and lipid-Associated states. J. Mol. Biol. 307, 1061-1073
36. Zabrocki, P., Bastiaens, I., Delay, C., Bammens, T., Ghillebert, R., Pellens, K., De Virgilio, C., Van Leuven, F., and Winderickx, J. (2008) Phosphorylation, lipid raft interaction and traffic of-synuclein in a yeast model for Parkinson. Biochim. Biophys. Acta 1783, 1767-1780
37. Marley, J., Lu, M., and Bracken, C. (2001) A method for efficient isotopic labeling of recombinant proteins. J. Biomol. NMR 20, 71-75
38. Johnson, M., Coulton, A. T., Geeves, M. A., and Mulvihill, D. P. (2010) Targeted amino-terminal acetylation of recombinant proteins in E. coli. PLoS ONE 5, e15801
39. Bussell, R., Jr., and Eliezer, D. (2003) A structural and functional role for 11-mer repeats in-synuclein and other exchangeable lipid binding proteins. J. Mol. Biol. 329, 763-778
40. Ulmer, T. S., Bax, A., Cole, N. B., and Nussbaum, R. L. (2005) Structure and dynamics of micelle-bound human-synuclein. J. Biol. Chem. 280, 9595-9603
41. Emsley, L., and Bodenhausen, G. (1992) Optimization of shaped selective pulses for NMR using a quaternion description of their overall propagators. J. Magn. Reson. 97, 135-148
42. Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., and Bax, A. (1995) NMRPipe. A multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 6, 277-293
43. Johnson, B. A., and Blevins, R. A. (1994)NMRView. A computer program for the visualization and analysis ofNMRdata. J. Biomol.NMR4, 603-614
44. Bussell, R., Jr., and Eliezer, D. (2004) Effects of Parkinson's disease-linked mutations on the structure of lipid-Associated-synuclein. Biochemistry 43, 4810-4818
45. Pfefferkorn, C. M., and Lee, J. C. (2010) Tryptophan probes at the-synuclein and membrane interface. J. Phys. Chem. B 114, 4615-4622
46. Bodner, C. R., Maltsev, A. S., Dobson, C. M., and Bax, A. (2010) Differential phospholipid binding of-synuclein variants implicated in Parkinson's disease revealed by solution NMR spectroscopy. Biochemistry 49, 862-871
47. Borbat, P., Ramlall, T. F., Freed, J. H., and Eliezer, D. (2006) Inter-helix distances in lysophospholipid micelle-bound-synuclein from pulsed ESR measurements. J. Am. Chem. Soc. 128, 10004-10005
48. Bussell, R., Jr., Ramlall, T. F., and Eliezer, D. (2005) Helix periodicity, topology, and dynamics of membrane-Associated-synuclein. Protein Sci. 14, 862-872
49. Chandra, S., Chen, X., Rizo, J., Jahn, R., and Südhof, T. C. (2003) A broken-helix in folded-synuclein. J. Biol. Chem. 278, 15313-15318
50. Hejjaoui, M., Butterfield, S., Fauvet, B., Vercruysse, F., Cui, J., Dikiy, I., Prudent, M., Olschewski, D., Zhang, Y., Eliezer, D., and Lashuel, H. (2012) Elucidating the role of C-terminal post-translational modifications using protein semisynthesis strategies.-Synuclein phosphorylation at tyrosine 125. J. Am. Chem. Soc. 134, 5196-5210
51. Paleologou, K. E., Oueslati, A., Shakked, G., Rospigliosi, C. C., Kim, H.-Y., Lamberto, G. R., Fernandez, C. O., Schmid, A., Chegini, F., Gai, W. P., Chiappe, D., Moniatte, M., Schneider, B. L., Aebischer, P., Eliezer, D., Zweckstetter, M., Masliah, E., and Lashuel, H. A. (2010) Phosphorylation at Ser-87 is enhanced in synucleinopathies, inhibits-synuclein oligomerization, and influences synuclein-membrane interactions. J. Neurosci. 30, 3184-3198
52. Paleologou, K. E., Schmid, A. W., Rospigliosi, C. C., Kim, H.-Y., Lamberto, G. R., Fredenburg, R. A., Lansbury, P. T., Jr., Fernandez, C. O., Eliezer, D., Zweckstetter, M., and Lashuel, H. A. (2008) Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of-synuclein. J. Biol. Chem. 283, 16895-16905
53. Rohl, C. A., and Baldwin, R. L. (1997) Comparison of NH exchange and circular dichroism as techniques for measuring the parameters of the helix-coil transition in peptides. Biochemistry 36, 8435-8442
54. Jensen, M. B., Bhatia, V. K., Jao, C. C., Rasmussen, J. E., Pedersen, S. L., Jensen, K. J., Langen, R., and Stamou, D. (2011) Membrane curvature sensing by amphipathic helices.Asingle liposome study using-synuclein and annexin B12. J. Biol. Chem. 286, 42603-42614
55. Kjaer, L., Giehm, L., Heimburg, T., and Otzen, D. (2009) The influence of vesicle size and composition on-synuclein structure and stability. Biophys. J. 96, 2857-2870
56. Middleton, E. R., and Rhoades, E. (2010) Effects of curvature and composition on-synuclein binding to lipid vesicles. Biophys. J. 99, 2279-2288
57. Nuscher, B., Kamp, F., Mehnert, T., Odoy, S., Haass, C., Kahle, P. J., and Beyer, K. (2004)-Synuclein has a high affinity for packing defects in a bilayer membrane. A thermodynamics study. J. Biol. Chem. 279, 21966-21975
58. Pranke, I. M., Morello, V., Bigay, J., Gibson, K., Verbavatz, J.-M., Antonny, B., and Jackson, C. L. (2011)-Synuclein and ALPS motifs are membrane curvature sensors whose contrasting chemistry mediates selective vesicle binding. J. Cell Biol. 194, 89-103
59. Bodner, C. R., Dobson, C. M., and Bax, A. (2009) Multiple tight phospholipid-binding modes of-synuclein revealed by solution NMR spectroscopy. J. Mol. Biol. 390, 775-790
60. Braun, A. R., Sevcsik, E., Chin, P., Rhoades, E., Tristram-Nagle, S., and Sachs, J. N. (2012)-Synuclein induces both positive mean curvature and negative Gaussian curvature in membranes. J. Am. Chem. Soc. 134, 2613-2620
61. Lokappa, S. B., and Ulmer, T. S. (2011)-Synuclein populates both elongated and broken helix states on small unilamellar vesicles. J. Biol. Chem. 286, 21450-21457
62. Mizuno, N., Varkey, J., Kegulian, N. C., Hegde, B. G., Cheng, N., Langen, R., and Steven, A. C. (2012) Remodeling of lipid vesicles into cylindrical micelles by-synuclein in an extended-helical conformation. J. Biol. Chem. 287, 29301-29311
63. Ouberai, M. M., Wang, J., Swann, M. J., Galvagnion, C., Guilliams, T., Dobson, C. M., and Welland, M. E. (2013)-Synuclein senses lipid packing defects and induces lateral expansion of lipids leading to membrane remodeling. J. Biol. Chem. 288, 20883-20895
64. Dikiy, I., and Eliezer, D. (2012) Folding and misfolding of-synuclein on membranes. Biochim. Biophys. Acta 1818, 1013-1018
65. Eliezer, D. (2008) in Parkinson's Disease. Molecular and Therapeutic Insights from Model Systems (Nass, R., and Przedborski, S., eds) 1st Ed., pp. 575-595, Academic Press, New York
66. Georgieva, E. R., Ramlall, T. F., Borbat, P. P., Freed, J. H., and Eliezer, D. (2010) The lipid-binding domain of wild type and mutant-synuclein. Compactness and interconversion between the broken and extended helix forms. J. Biol. Chem. 285, 28261-28274
67. Georgieva, E. R., Ramlall, T. F., Borbat, P. P., Freed, J. H., and Eliezer, D. (2008) Membrane-bound-synuclein forms an extended helix Long-distance pulsed ESR measurements using vesicles, bicelles, and rodlike micelles. J. Am. Chem. Soc. 130, 12856-12857
68. Jo, E., Darabie, A. A., Han, K., Tandon, A., Fraser, P. E., and McLaurin, J. (2004)-Synuclein-synaptosomal membrane interactions. Implications for fibrillogenesis. Eur. J. Biochem. 271, 3180-3189
69. Necula, M., Chirita, C. N., and Kuret, J. (2003) Rapid anionic micellemediated-synuclein fibrillization in vitro. J. Biol. Chem. 278, 46674-46680
70. Perrin, R. J., Woods, W. S., Clayton, D. F., and George, J. M. (2001) Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins. J. Biol. Chem. 276, 41958-41962
71. Chakrabartty, A., Doig, A. J., and Baldwin, R. L. (1993) Helix capping propensities in peptides parallel those in proteins. Proc. Natl. Acad. Sci. U.S.A. 90, 11332-11336
72. Maison, W., Arce, E., Renold, P., Kennedy, R. J., and Kemp, D. S. (2001) Optimal N-caps for N-terminal helical templates. Effects of changes in H-bonding efficiency and charge. J. Am. Chem. Soc. 123, 10245-10254
73. Bartels, T., Ahlstrom, L. S., Leftin, A., Kamp, F., Haass, C., Brown, M. F., and Beyer, K. (2010) The N-terminus of the intrinsically disordered protein-synuclein triggers membrane binding and helix folding. Biophys. J. 99, 2116-2124
74. Ferreon, A. C., Gambin, Y., Lemke, E. A., and Deniz, A. A. (2009) Interplay of-synuclein binding and conformational switching probed by singlemolecule fluorescence. Proc. Natl. Acad. Sci. U.S.A. 106, 5645-5650
75. Varkey, J., Mizuno, N., Hegde, B. G., Cheng, N., Steven, A. C., and Langen, R. (2013)-Synuclein oligomers with broken helical conformation form lipoprotein nanoparticles. J. Biol. Chem. 288, 17620-17630
76. Junge, F., Schneider, B., Reckel, S., Schwarz, D., Dötsch, V., and Bernhard, F. (2008) Large-scale production of functional membrane proteins. Cell. Mol. Life Sci. 65, 1729-1755
77. Tulumello, D. V., and Deber, C. M. (2012) Efficiency of detergents at maintaining membrane protein structures in their biologically relevant forms. Biochim. Biophys. Acta 1818, 1351-1358
78. Tanford, C. (1980) The Hydrophobic Effect. Formation of Micelles and Biological Membranes, 2nd Ed., John Wiley & Sons, Inc., New York
79. Drescher, M., Godschalk, F., Veldhuis, G., van Rooijen, B. D., Subramaniam, V., and Huber, M. (2008) Spin-label EPR on-synuclein reveals differences in the membrane binding affinity of the two antiparallel helices. Chembiochem 9, 2411-2416
80. Anderson, V. L., Ramlall, T. F., Rospigliosi, C. C., Webb, W. W., and Eliezer, D. (2010) Identification of a helical intermediate in trifluoroethanol-induced-synuclein aggregation. Proc. Natl. Acad. Sci. U.S.A. 107, 18850-18855
81. Takamori, S., Holt, M., Stenius, K., Lemke, E. A., Grønborg, M., Riedel, D., Urlaub, H., Schenck, S., Brügger, B., Ringler, P.,Müller, S. A., Rammner, B., Gräter, F., Hub, J. S., De Groot, B. L., Mieskes, G., Moriyama, Y., Klingauf, J., Grubmüller, H., Heuser, J., Wieland, F., and Jahn, R. (2006) Molecular anatomy of a trafficking organelle. Cell 127, 831-846
82. Kamp, F., and Beyer, K. (2006) Binding of-synuclein affects the lipid packing in bilayers of small vesicles. J. Biol. Chem. 281, 9251-9259
83. Varkey, J., Isas, J. M., Mizuno, N., Jensen, M. B., Bhatia, V. K., Jao, C. C., Petrlova, J., Voss, J. C., Stamou, D. G., Steven, A. C., and Langen, R. (2010) Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins. J. Biol. Chem. 285, 32486-32493
84. Seelig, J. (2004) Thermodynamics of lipid-peptide interactions. Biochim. Biophys. Acta 1666, 40-50