Effect of dioxygen on copper(II) binding to alpha-synuclein
Heather R Lucas1, Jennifer C Lee
1Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-8013, United States.
Journal of Inorganic Biochemistry
|January 13, 2010
Summary
Copper(II) binding to alpha-synuclein is significantly enhanced by oxygen, with binding affinity increasing tenfold. Methionine oxidation does not alter copper-peptide conformation, suggesting a potential copper-tryptophan interaction.
Area of Science:
- Biochemistry
- Protein-metal interactions
- Spectroscopy
Background:
- Alpha-synuclein is implicated in neurodegenerative diseases.
- Copper(II) binding to alpha-synuclein is relevant to its function and aggregation.
- Tryptophan fluorescence is a sensitive probe for protein-metal interactions.
Purpose of the Study:
- To characterize copper(II) binding to F4W alpha-synuclein.
- To investigate the effect of dioxygen on copper(II) binding.
- To explore the role of methionine oxidation in copper-peptide interactions.
Main Methods:
- Fluorescent amino acid tryptophan (Trp) spectroscopy.
- Circular dichroism (CD) spectroscopy.
- Use of synthetic peptide models with and without methionine oxidation.
Main Results:
- Copper(II) binding to F4W alpha-synuclein is enhanced by dioxygen (K(d(app))) from 100 nM to 10 nM.
- Phenyl-to-indole substitution (F-->W) does not alter copper(II) binding or stoichiometry.
- Methionine oxidation does not affect copper-peptide conformation.
- A potential Cu(II)-Trp/Phe (cation-pi) interaction is suggested.
Conclusions:
- Oxygen significantly enhances copper(II) binding to alpha-synuclein.
- Methionine oxidation is not a major factor in copper-peptide conformation.
- The study provides insights into the structural and binding properties of copper-alpha-synuclein complexes.
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