A revised picture of the Cu(II)-α-synuclein complex: The role of N-terminal acetylation

Gina M. Moriarty, Conceição A.S.A. Minetti, David P. Remeta, Jean Baum

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

α-Synuclein (αS) is an amyloidogenic intrinsically disordered protein implicated in Parkinson's disease, for which copper-mediated pathways of neurodegeneration have been suggested. We have employed nuclear magnetic resonance, circular dichroism, electrospray ionization mass spectrometry, and thioflavin T fluorescence to characterize interactions of Cu2+ with the physiological acetylated form (Ac-αS). Significantly, N-terminal acetylation abolishes Cu2+ binding at the high-affinity M1-D2 site present in the nonacetylated protein and maintains Cu2+ interactions around H50/D121. Fibrillation enhancement observed at an equimolar Cu 2+ stoichiometry with the nonacetylated model does not occur with Ac-αS. These findings open new avenues of investigation into Cu 2+-mediated neurodegenerative pathology suggested in vivo.

Original languageEnglish (US)
Pages (from-to)2815-2817
Number of pages3
JournalBiochemistry
Volume53
Issue number17
DOIs
StatePublished - May 6 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry

Fingerprint

Dive into the research topics of 'A revised picture of the Cu(II)-α-synuclein complex: The role of N-terminal acetylation'. Together they form a unique fingerprint.

Cite this