ArticleProtein science : a publication of the Protein Society2024
Copper ion incorporation in α-synuclein amyloids.
Article in Protein science : a publication of the Protein Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Pooled it
- Atmospheric Aerosol Neurotoxicity and Parkinson's Disease: Mechanisms and Perspectives.Journal of biochemical and molecular toxicology · 2026Review
- Curcumin Attenuates Cuproptosis via Activating Autophagy Through Inhibition of the AKT/mTOR/P70S6K-Signaling Pathway in Parkinson's Disease Models.Molecular neurobiology · 2026Article
- Time-Resolved SAXS Reveals Distinct Millisecond Metal-Induced Conformational Dynamics of Monomeric α-Synuclein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Context-dependent ATP7 Interactions with Parkinson's Disease-associated Genes Modulate Copper Homeostasis Phenotypes.bioRxiv : the preprint server for biology · 2026Article
- Navigating Transition Metal-Dependent Cell Death: Mechanisms, Crosstalk, and Future Directions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- CAPIM: Catalytic activity and site prediction and analysis tool in multimer proteins.Protein science : a publication of the Protein Society · 2025Article
- Article
- Linking Parkinson's disease and melanoma: the impact of copper-driven cuproptosis and related mechanisms.NPJ Parkinson's disease · 2025Article
- Article
- Improved Large-Scale Synthesis of Acridonylalanine for Diverse Peptide and Protein Applications.Bioconjugate chemistry · 2024Article
- Primary Nucleation of Polymorphic α-Synuclein Dimers Depends on Copper Concentrations and Definite Copper-Binding Site.Biomolecules · 2024Article
- Copper ion incorporation in α-synuclein amyloids.Protein science : a publication of the Protein Society · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Copper ion dys-homeostasis is linked to neurodegenerative diseases involving amyloid formation. Even if many amyloidogenic proteins can bind copper ions as monomers, little is known about copper interactions with the resulting amyloid fibers. Here, we investigate copper interactions with α-synuclein, the amyloid-forming protein in Parkinson's disease. Copper (Cu(II)) binds tightly to monomeric α-synuclein in vitro involving the N-terminal amine and the side chain of His50. Using purified protein and biophysical methods in vitro, we reveal that copper ions are readily incorporated into the formed amyloid fibers when present at the start of aggregation reactions, and the metal ions also bind if added to pre-formed amyloids. Efficient incorporation is observed for α-synuclein variants with perturbation of either one of the high-affinity monomer copper-binding residues (i.e., N-terminus or His50) whereas a variant with both N-terminal acetylation and His50 substituted with Ala does not incorporate any copper into the amyloids. Both the morphology of the resulting α-synuclein amyloids (amyloid fiber pitch, secondary structure, proteinase sensitivity) and the copper chemical properties (redox activity, chemical potential) are altered when copper is incorporated into amyloids. We speculate that copper chelation by α-synuclein amyloids contributes to the observed copper dys-homeostasis (e.g., reduced bioavailable levels) in Parkinson's disease patients. At the same time, amyloid-copper interactions may be protective to neuronal cells as they will shield aberrantly free copper ions from promotion of toxic reactive oxygen species.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.