Quantification of the Binding Properties of Cu2+ to the Amyloid Beta Peptide: Coordination Spheres for Human and Rat Peptides and Implication on Cu2+-Induced Aggregation
| Autor: | John D. Simon, Christopher G. Dudzik, Glenn L. Millhauser, Lian Hong, William D. Bush, Tessa M. Carducci |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
inorganic chemicals
Circular dichroism Coordination sphere Stereochemistry Molecular Sequence Data Peptide Plasma protein binding Calorimetry Ligands Article law.invention Metal law Materials Chemistry Animals Humans Amino Acid Sequence Physical and Theoretical Chemistry Electron paramagnetic resonance Peptide sequence chemistry.chemical_classification Amyloid beta-Peptides Circular Dichroism Electron Spin Resonance Spectroscopy Isothermal titration calorimetry Hydrogen-Ion Concentration Rats Surfaces Coatings and Films Crystallography chemistry visual_art Mutation visual_art.visual_art_medium Thermodynamics Copper Protein Binding |
| Zdroj: | The Journal of Physical Chemistry B. 114:11261-11271 |
| ISSN: | 1520-5207 1520-6106 |
| Popis: | There is no consensus on the coordinating ligands for Cu(2+) by Abeta. However, the differences in peptide sequence between human and rat have been hypothesized to alter metal ion binding in a manner that alters Cu(2+)-induced aggregation of Abeta. Herein, we employ isothermal titration calorimetry (ITC), circular dichroism (CD), and electron paramagnetic resonance (EPR) spectroscopy to examine the Cu(2+) coordination spheres to human and rat Abeta and an extensive set of Abeta(16) mutants. EPR of the mutant peptides is consistent with a 3N1O binding geometry, like the native human peptide at pH 7.4. The thermodynamic data reveal an equilibrium between three coordination spheres, {NH(2), O, N(Im)(His6), N(-)}, {NH(2), O, N(Im)(His6), N(Im)(His13)}, and {NH(2), O, N(Im)(His6), N(Im)(His14)}, for human Abeta(16) but one dominant coordination for rat Abeta(16), {NH(2), O, N(Im)(His6), N(-)}, at pH 7.4-6.5. ITC and CD data establish that the mutation R5G is sufficient for reproducing this difference in Cu(2+) binding properties at pH 7.4. The substitution of bulky and positively charged Arg by Gly is proposed to stabilize the coordination {NH(2), O-, N(Im)(His6), N(-)} that then results in one dominating coordination sphere for the case of the rat peptide. The differences in the coordination geometries for Cu(2+) by the human and rat Abeta are proposed to contribute to the variation in the ability of Cu(2+) to induce aggregation of Abeta peptides. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|