This title appears in the Scientific Report :
2015
Please use the identifier:
http://dx.doi.org/10.1021/jacs.5b01911 in citations.
Copper Binding to the N-Terminally Acetylated, Naturally Occurring Form of Alpha-Synuclein Induces Local Helical Folding
Copper Binding to the N-Terminally Acetylated, Naturally Occurring Form of Alpha-Synuclein Induces Local Helical Folding
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...
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Personal Name(s): | Miotto, Marco C. |
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Valiente-Gabioud, Ariel A. / Rossetti, Giulia / Zweckstetter, Markus / Carloni, Paolo / Selenko, Philipp / Griesinger, Christian / Binolfi, Andres (Corresponding author) / Fernández, Claudio O. (Corresponding author) | |
Contributing Institute: |
Jülich Supercomputing Center; JSC Computational Biomedicine; IAS-5 GRS; GRS |
Published in: | Journal of the American Chemical Society, 137 (2015) 20, S. 6444 - 6447 |
Imprint: |
Washington, DC
American Chemical Society
2015
|
PubMed ID: |
25939020 |
DOI: |
10.1021/jacs.5b01911 |
Document Type: |
Journal Article |
Research Program: |
Computational Science and Mathematical Methods |
Publikationsportal JuSER |
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. |