title: Zinc binding agonist effect on the recognition of the beta-amyloid (4-10) epitope by anti-beta-amyloid antibodies.
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.
authors.affiliation: Department of Regulations, Development and Molecular Diversity, USM 502, UMR 5154, CNRS Chemistry and Biochemistry of Natural Substances, National Museum of Natural History, 63 rue Buffon, 75231 Paris Cedex 05, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Zirah
authors.forename: Raluca
authors.initials: R
authors.lastname: Stefanescu
authors.forename: Marilena
authors.initials: M
authors.lastname: Manea
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Tian
authors.forename: Roxana
authors.initials: R
authors.lastname: Cecal
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Kozin
authors.forename: Pascale
authors.initials: P
authors.lastname: Debey
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rebuffat
authors.forename: Michael
authors.initials: M
authors.lastname: Przybylski
mesh_terms: D016229:Amyloid beta-Peptides / Q000819:agonists* / Q000276:immunology* / Q000378:metabolism; D000906:Antibodies / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D008670:Metals / Q000378:metabolism / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D000939:Epitopes; D008670:Metals; D015032:Zinc