Zinc binding agonist effect on the recognition of the β-amyloid (4–10) epitope by anti-β-amyloid antibodies
- 20 August 2004
- journal article
- Published by Elsevier BV in Biochemical and Biophysical Research Communications
- Vol. 321 (2), 324-328
- https://doi.org/10.1016/j.bbrc.2004.06.150
Abstract
Amyloid plaques associated to Alzheimer's disease present a high content of zinc ions. We previously showed that the N-terminal region of the amyloid peptide Abeta constitutes an autonomous zinc-binding domain. This region encompasses the previously identified epitope Abeta(4-10) targeted by antibodies capable to reduce amyloid deposition, but the influence of Abeta/Zn binding on the epitope recognition remains unknown. We demonstrate here the effect of Zn2+ ions on the recognition of peptides sharing the sequence of the Abeta N-terminal domain, by two monoclonal antibodies recognizing the beta-amyloid(4-10) epitope. The presence of Zn2+, but not of other cations, increased the recognition of the (1-16) peptide, while it was without effect on the recognition of the (1-10) peptide. These findings show a zinc-induced conformational change of the (1-16)-N-terminal region of AP3, which results in a better accessibility of the Abeta(4-10) epitope to the anti-Abeta antibodies, and suggest a role of zinc in epitope-based vaccination approaches.Keywords
This publication has 32 references indexed in Scilit:
- A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMRProceedings of the National Academy of Sciences of the United States of America, 2002
- Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's diseaseEssays in Biochemistry, 2002
- Alzheimer’s amyloid fibrils: structure and assemblyBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2000
- Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivativesPhysiological Reviews, 1997
- Surfactant properties of Alzheimer's A beta peptides and the mechanism of amyloid aggregation.Journal of Biological Chemistry, 1994
- Rapid induction of Alzheimer A beta amyloid formation by zincScience, 1994
- Aluminum, Iron, and Zinc Ions Promote Aggregation of Physiological Concentrations of β‐Amyloid PeptideJournal of Neurochemistry, 1993
- Production of the Alzheimer Amyloid β Protein by Normal Proteolytic ProcessingScience, 1992
- Isolation and quantification of soluble Alzheimer's β-peptide from biological fluidsNature, 1992
- Amyloid β-peptide is produced by cultured cells during normal metabolismNature, 1992