A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein

Gandhi, Neha S., Landrieu, I., Byrne, C., Kukic, P., Amniai, L., Cantrelle, F. X., Wieruszeski, J. M., Mancera, R. L., Jacquot, Y., & Lippens, G. (2015) A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein. Angewandte Chemie - International Edition, 54(23), pp. 6923-6927.

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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.

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ID Code: 93827
Item Type: Journal Article
Refereed: Yes
DOI: 10.1002/anie.201501898
ISSN: 1433-7851
Copyright Owner: Copyright 2015 Wiley
Deposited On: 30 Mar 2016 02:14
Last Modified: 30 Mar 2016 21:21

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