Copper Binding to the N‑Terminally Acetylated, Naturally Occurring Form of Alpha-Synuclein Induces Local Helical Folding
- Miotto, Marco César
- Valiente Gabioud, Ariel Alejandro
- Rossetti, Giulia
- Zweckstetter, Markus
- Carloni, Paolo
- Selenko, Philipp
- Griesinger, Christian
- Binolfi, Andrés
- Fernandez, Claudio Oscar
DOIAbstract
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.Fil: Miotto, Marco César. C...
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