A Phosphorylation-Induced Turn Defines the Alzheimer's Disease AT8 Antibody Epitope on the Tau Protein.

Abstract

Post mortem biochemical staging of Alzheimer's disease is currently based on immunochemical analysis of brain slices with the AT8 antibody. The epitope of AT8 is described around the pSer202/pThr205 region of the hyperphosphorylated form of the neuronal protein tau. In this study, NMR spectroscopy was used to precisely map the AT8 epitope on phosphorylated tau, and derive its defining structural features by a combination of NMR analyses and molecular dynamics. A particular turn conformation is stabilized by a hydrogen bond of the phosphorylated Thr205 residue to the amide proton of Gly207, and is further stabilized by the two Arg residues opposing the pSer202/pThr205.

• Authors: Neha S Gandhi, Isabelle Landrieu, Cillian Byrne, Predrag Kukic, Laziza Amniai, François-Xavier Cantrelle, Jean-Michel Wieruszeski, Ricardo L Mancera, Yves Jacquot, Guy Lippens
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 54 Issue 23 Pg. 6819-23 (Jun 01 2015) ISSN: 1521-3773 [Electronic] Germany
• PMID: 25881502 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antibodies, Monoclonal
• Epitopes
• tau Proteins

Topics

• Alzheimer Disease (immunology, metabolism)
• Antibodies, Monoclonal (immunology)
• Epitope Mapping
• Epitopes (chemistry, immunology)
• Humans
• Molecular Dynamics Simulation
• Nuclear Magnetic Resonance, Biomolecular
• Phosphorylation
• tau Proteins (chemistry, immunology, metabolism)