Abstract
Arising from T. Bartels, J. G. Choi & D. J. Selkoe. Nature 477, 107–110 (2011).10.1038/nature10324
α-Synuclein is an abundant presynaptic protein that binds to negatively charged phospholipids1,2, functions as a SNARE-complex chaperone3 and contributes to Parkinson’s disease pathogenesis4,5. Recombinant α-synuclein in solution is largely unfolded and devoid of tertiary structure6,7,8,9,10,11, but Bartels et al.12 have proposed that native α-synuclein purified from human erythrocytes forms a stably folded, soluble tetramer that resists aggregation. By contrast, we show here that native α-synuclein purified from mouse brain consists of a largely unstructured monomer, exhibits no stable tetramer formation, and is prone to aggregation. The native state of α-synuclein is important for understanding its pathological effects as a stably folded protein would be much less prone to aggregation than a conformationally labile protein. There is a Reply to this Brief Communication Arising by Bartels, T. & Selkoe, D. J. Nature 498, http://dx.doi.org/10.1038/nature12126 (2013).
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References
Davidson, W. S., Jonas, A., Clayton, D. F. & George, J. M. Stabilization of α-Synuclein secondary structure upon binding to synthetic membranes. J. Biol. Chem. 273, 9443–9449 (1998)
Jo, E., McLaurin, J., Yip, C. M., St George-Hyslop, P. & Fraser, P. E. α-Synuclein membrane interactions and lipid specificity. J. Biol. Chem. 275, 34328–34334 (2000)
Burré, J. et al. α-Synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329, 1663–1667 (2010)
Martin, I., Dawson, V. L. & Dawson, T. M. Recent advances in the genetics of Parkinson’s disease. Annu. Rev. Genomics Hum. Genet. 12, 301–325 (2011)
Devine, M. J., Gwinn, K., Singleton, A. & Hardy, J. Parkinson’s disease and α-synuclein expression. Mov. Disord. 26, 2160–2168 (2011)
Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A. & Lansbury, P. T., Jr NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry 35, 13709–13715 (1996)
Kim, J. Evidence that the precursor protein of non-A beta component of Alzheimer's disease amyloid (NACP) has an extended structure primarily composed of random-coil. Mol. Cells 7, 78–83 (1997)
Uversky, V. N., Lee, H. J., Li, J., Fink, A. L. & Lee, S. J. Stabilization of partially folded conformation during α-synuclein oligomerization in both purified and cytosolic preparations. J. Biol. Chem. 276, 43495–43498 (2001)
Chandra, S., Chen, X., Rizo, J., Jahn, R. & Südhof, T. C. A broken α-helix in folded α-synuclein. J. Biol. Chem. 278, 15313–15318 (2003)
Lokappa, S. B. & Ulmer, T. S. α-Synuclein populates both elongated and broken helix states on small unilamellar vesicles. J. Biol. Chem. 286, 21450–21457 (2011)
Fauvet, B. et al. α-synuclein in the central nervous system and from erythrocytes, mammalian cells and E. coli exists predominantly as a disordered monomer. J. Biol. Chem. 287, 15345–15364 (2012)
Bartels, T., Choi, J. G. & Selkoe, D. J. α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477, 107–110 (2011)
Maltsev, A. S., Ying, J. & Bax, A. Impact of N-terminal acetylation of α-synuclein on its random coil and lipid binding properties. Biochemistry 51, 5004–5013 (2012)
Johnson, H. & Eyers, C. E. Analysis of post-translational modifications by LC-MS/MS. Methods Mol. Biol. 658, 93–108 (2010)
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J.B., S.V., J.D. and M.S. performed the experiments. All authors planned and analysed the experiments and wrote the paper.
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Burré, J., Vivona, S., Diao, J. et al. Properties of native brain α-synuclein. Nature 498, E4–E6 (2013). https://doi.org/10.1038/nature12125
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DOI: https://doi.org/10.1038/nature12125
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