期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 54, 期 23, 页码 6819-6823出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201501898
关键词
Alzheimer's disease; AT8 antibody; epitope mapping; phosphorylation; tau protein
资金
- ANR (program MALZ-TAF)
- LabEx Distalz grant (France)
- Curtin Early Research fellowship
- Australian Government
- Government of Western Australia
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 pSer(202)/pThr(205) 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 Thr(205) residue to the amide proton of Gly(207), and is further stabilized by the two Arg residues opposing the pSer(202)/pThr(205).
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