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

J Am Chem Soc. 2015 May 27;137(20):6444-7. doi: 10.1021/jacs.5b01911. Epub 2015 May 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Binding Sites
  • Copper / chemistry*
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Organometallic Compounds / chemistry*
  • Protein Folding
  • alpha-Synuclein / chemistry*

Substances

  • Organometallic Compounds
  • alpha-Synuclein
  • Copper