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Updated: Jul 5, 2026
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Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
Copper(II) binding to alpha-synuclein, the Parkinson's protein
Jennifer C Lee1, Harry B Gray, Jay R Winkler
1Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-8013, USA. leej4@mail.nih.gov
Journal of the American Chemical Society
|May 10, 2008
Summary
Copper(II) ions bind tightly to alpha-synuclein, a protein linked to Parkinson's disease. This interaction occurs near the protein's N-terminus and does not involve histidine at position 50.
Area of Science:
- Biochemistry
- Neuroscience
- Protein Chemistry
Background:
- Alpha-synuclein is a protein associated with Parkinson's disease.
- Understanding protein-metal interactions is crucial for neurodegenerative disease research.
Purpose of the Study:
- To investigate the interaction between copper(II) and alpha-synuclein.
- To identify the binding site and affinity of copper(II) to alpha-synuclein.
Main Methods:
- Tryptophan fluorescence intensity and decay kinetics measurements.
- Site-directed mutagenesis (F4W and F4W/H50S mutants).
Main Results:
- Copper(II) interacts with alpha-synuclein, confirmed by fluorescence variations.
- High-affinity binding of Cu(II) (Kd = 100 nM) near the N-terminus at pH 7.
- Histidine at position 50 is not involved in the high-affinity copper binding site.
Conclusions:
- Copper(II) binds specifically to alpha-synuclein near the N-terminus.
- This binding is independent of histidine at position 50.
- Findings contribute to understanding alpha-synuclein's role in Parkinson's disease pathogenesis.
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