Supramolecular Modulation of Structural Polymorphism in Pathogenic α-Synuclein Fibrils Using Copper(II) Coordination

Tae Su Choi, Jeeyoung Lee, Jong Yoon Han, Byung Chul Jung, Piriya Wongkongkathep, Joseph A. Loo, Min Jae Lee, Hugh I. Kim

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14 Citations (Scopus)


Structural variation of α-synuclein (αSyn) fibrils has been linked to the diverse etiologies of synucleinopathies. However, little is known about what specific mechanism provides αSyn fibrils with pathologic features. Herein, we demonstrate Cu(II)-based supramolecular approach for unraveling the formation process of pathogenic αSyn fibrils and its application in a neurotoxic mechanism study. The conformation of αSyn monomer was strained by macrochelation with Cu(II), thereby disrupting the fibril elongation while promoting its nucleation. This non-canonical process formed shortened, β-sheet enriched αSyn fibrils (<0.2 μm) that were rapidly transmitted and accumulated to neuronal cells, causing neuronal cell death, in sharp contrast to typical αSyn fibrils (ca. 1 μm). Our approach provided the supramolecular basis for the formation of pathogenic fibrils through physiological factors, such as brain Cu(II).

Original languageEnglish
Pages (from-to)3099-3103
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number12
Publication statusPublished - 2018 Mar 12



  • fibril strain
  • mass spectrometry
  • Parkinson's disease
  • small-angle X-ray scattering
  • transition metals

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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