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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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
Volume57
Issue number12
DOIs
Publication statusPublished - 2018 Mar 12

Fingerprint

Synucleins
Cell death
Polymorphism
Conformations
Copper
Elongation
Brain
Nucleation
Monomers
Modulation

Keywords

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

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

Supramolecular Modulation of Structural Polymorphism in Pathogenic α-Synuclein Fibrils Using Copper(II) Coordination. / Choi, Tae Su; Lee, Jeeyoung; Han, Jong Yoon; Jung, Byung Chul; Wongkongkathep, Piriya; Loo, Joseph A.; Lee, Min Jae; Kim, Hugh I.

In: Angewandte Chemie - International Edition, Vol. 57, No. 12, 12.03.2018, p. 3099-3103.

Research output: Contribution to journalArticle

Choi, Tae Su ; Lee, Jeeyoung ; Han, Jong Yoon ; Jung, Byung Chul ; Wongkongkathep, Piriya ; Loo, Joseph A. ; Lee, Min Jae ; Kim, Hugh I. / Supramolecular Modulation of Structural Polymorphism in Pathogenic α-Synuclein Fibrils Using Copper(II) Coordination. In: Angewandte Chemie - International Edition. 2018 ; Vol. 57, No. 12. pp. 3099-3103.
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