Copper binding to the N-terminally acetylated, naturally occurring form of 
alpha-synuclein induces local helical folding.

Miotto, M. C.; Valiente-Gabioud, A. A.; Rossetti, G.; Zweckstetter, M.; Carloni, P.; Selenko, P.; Griesinger, C.; Binolfi, A.; Fernández, C. O.

doi:10.1021/jacs.5b01911

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Journal Article

Copper binding to the N-terminally acetylated, naturally occurring form of alpha-synuclein induces local helical folding.

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Zweckstetter, M.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

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Griesinger, C.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

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http://pubs.acs.org/doi/pdf/10.1021/jacs.5b01911
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Citation

Miotto, M. C., Valiente-Gabioud, A. A., Rossetti, G., Zweckstetter, M., Carloni, P., Selenko, P., et al. (2015). Copper binding to the N-terminally acetylated, naturally occurring form of alpha-synuclein induces local helical folding. Journal of the American Chemical Society, 137(20), 6444-6447. doi:10.1021/jacs.5b01911.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0027-7D83-C

Abstract

Growing evidence supports a link between brain copper homeostasis, the formation of alpha-synuclein (AS)-copper complexes, and the development of Parkinson disease (PD). Recently it was demonstrated that the physiological form of AS is N-terminally acetylated (AcAS). Here we used NMR spectroscopy to structurally characterize the interaction between Cu(I) and AcAS. We found that the formation of an AcAS–Cu(I) complex at the N-terminal region stabilizes local conformations with α-helical secondary structure and restricted motility. Our work provides new evidence into the metallo-biology of PD and opens new lines of research as the formation of AcAS–Cu(I) complex might impact on AcAS membrane binding and aggregation.