Supramolecular Modulation of Structural Polymorphism in Pathogenic α-Synuclein Fibrils Using Copper(II) Coordination
| Autor: | Hugh I. Kim, Jong Yoon Han, Byung Chul Jung, Joseph A. Loo, Piriya Wongkongkathep, Min Jae Lee, Tae Su Choi, Jee Young Lee |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Programmed cell death Macromolecular Substances Protein Conformation Supramolecular chemistry chemistry.chemical_element macromolecular substances Fibril Catalysis chemistry.chemical_compound 03 medical and health sciences Protein structure 0302 clinical medicine Tumor Cells Cultured Animals Humans Synucleinopathies Neurons Polymorphism Genetic General Chemistry General Medicine Copper Rats Monomer 030104 developmental biology Polymorphism (materials science) chemistry Biophysics alpha-Synuclein 030217 neurology & neurosurgery |
| Zdroj: | Angewandte Chemie (International ed. in English). 57(12) |
| ISSN: | 1521-3773 |
| Popis: | 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 ( |
| Databáze: | OpenAIRE |
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