TY - JOUR
T1 - A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein
AU - Gandhi, Neha S.
AU - Landrieu, Isabelle
AU - Byrne, Cillian
AU - Kukic, Predrag
AU - Amniai, Laziza
AU - Cantrelle, François Xavier
AU - Wieruszeski, Jean Michel
AU - Mancera, Ricardo L.
AU - Jacquot, Yves
AU - Lippens, Guy
N1 - Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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. The AT8 epitope of the phosphorylated tau protein was mapped by NMR spectroscopy, and its defining structural features were derived by a combination of NMR analyses and molecular dynamics. A particular turn conformation is stabilized by a hydrogen bond of the phosphorylated Thr205 residue (pThr205) to the amide proton of Gly207.
AB - 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. The AT8 epitope of the phosphorylated tau protein was mapped by NMR spectroscopy, and its defining structural features were derived by a combination of NMR analyses and molecular dynamics. A particular turn conformation is stabilized by a hydrogen bond of the phosphorylated Thr205 residue (pThr205) to the amide proton of Gly207.
UR - https://www.scopus.com/pages/publications/84930508317
UR - https://www.scopus.com/inward/citedby.url?scp=84930508317&partnerID=8YFLogxK
U2 - 10.1002/anie.201501898
DO - 10.1002/anie.201501898
M3 - Article
C2 - 25881502
AN - SCOPUS:84930508317
SN - 1433-7851
VL - 54
SP - 6819
EP - 6823
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 23
ER -