title: 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.affiliation: School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Perth (Australia).
authors.forename: Neha S
authors.initials: NS
authors.lastname: Gandhi
authors.affiliation: CNRS UMR 8576, University of Lille 1 (France).
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landrieu
authors.affiliation: CNRS UMR 7203, Université Pierre et Marie Curie, Ecole Normale Supérieure, Paris (France).|Institut Baulieu, Kremlin-Bicêtre (France).
authors.forename: Cillian
authors.initials: C
authors.lastname: Byrne
authors.affiliation: Department of Chemistry, Cambridge University, Cambridge (UK).
authors.forename: Predrag
authors.initials: P
authors.lastname: Kukic
authors.affiliation: CNRS UMR 8576, University of Lille 1 (France).
authors.forename: Laziza
authors.initials: L
authors.lastname: Amniai
authors.affiliation: CNRS UMR 8576, University of Lille 1 (France).
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Cantrelle
authors.affiliation: CNRS UMR 8576, University of Lille 1 (France).
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Wieruszeski
authors.affiliation: School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Perth (Australia).
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Mancera
authors.affiliation: CNRS UMR 7203, Université Pierre et Marie Curie, Ecole Normale Supérieure, Paris (France).
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacquot
authors.affiliation: CNRS UMR 8576, University of Lille 1 (France). Guy.Lippens@univ-lille1.fr.
authors.forename: Guy
authors.initials: G
authors.lastname: Lippens
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D016875:tau Proteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D016875:tau Proteins
keywords: AT8 antibody; Alzheimer’s disease; epitope mapping; phosphorylation; tau protein