磷酸化诱导的构象变化决定了 Tau 蛋白上阿尔茨海默病 AT8 抗体的抗原表位。
A Phosphorylation-Induced Turn Defines the Alzheimer's Disease AT8 Antibody Epitope on the Tau Protein.
机构信息
School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Perth (Australia).
CNRS UMR 8576, University of Lille 1 (France).
出版信息
Angew Chem Int Ed Engl. 2015 Jun 1;54(23):6819-23. doi: 10.1002/anie.201501898. Epub 2015 Apr 16.
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.
目前，阿尔茨海默病的死后生化分期是基于用 AT8 抗体对脑切片进行免疫化学分析。AT8 的表位被描述为神经元蛋白 tau 的高度磷酸化形式周围的 pSer202/pThr205 区域。在这项研究中，使用 NMR 光谱精确绘制了磷酸化 tau 上的 AT8 表位，并通过 NMR 分析和分子动力学的组合得出其定义结构特征。磷酸化 Thr205 残基与 Gly207 的酰胺质子之间的氢键稳定了一个特定的转角构象，并且进一步由两个 Arg 残基稳定，这两个 Arg 残基与 pSer202/pThr205 相对。
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