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

MARCO C. MIOTTO; ARIEL A. VALIENTE-GABIOUD; JULIA ROSSETTI; MARKUS ZWECKSTETTER; PAOLO CARLONI; PHILIPP SELENKO; CHRISTIAN GRIESINGER; ANDRÉS BINOLFI*; CLAUDIO O. FERNÁNDEZ*

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2015

0002-7863

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.