A serine-->proline change in the Alzheimer's disease-associated epitope Tau 2 results in altered secondary structure, but phosphorylation overcomes the conformational gap.

A serine-->proline change in the Alzheimer's disease-associated epitope Tau 2 results in altered secondary structure, but phosphorylation overcomes the conformational gap.
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阿尔茨海默病相关表位 Tau 2 中的丝氨酸→脯氨酸变化导致二级结构改变,但磷酸化克服了构象间隙。

DOI:
10.1016/0006-291x(92)92364-4
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发表时间:
1992
影响因子:
3.1
通讯作者:
OtvosJr,L
OtvosJr,L
中科院分区:
生物学4区
文献类型:
--
作者:
Lang,E;OtvosJr,L

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针对牛ti蛋白的单克隆抗体Tau 2被提出,据报道识别构象表位,并且在阿尔茨海默病的神经元缠结中发现染色的τ,而不是正常人τ。我们合成了与原始牛序列、其丝氨酸→脯氨酸取代的类似物、该区域的真正人类序列以及在关键的丝氨酸上磷酸化的牛表位相对应的四肽。用圆二色谱法测定了多肽的二级结构。发现只有原始牛表位显示出形成神经元缠结特征性的β-折叠片的趋势。人肽、其类似物β和磷酸化牛序列的光谱非常相似,具有弱螺旋β-转角特征。这种严重磷酸化的蛋白质的表位的最终磷酸化可以克服种间构象间隙。
Monoclonal antibody Tau 2 was raised against bovine ti protein, was reported to to recognize a conformational epitope, and stainedτ was found in neurofibrillary tangles of Alzheimer's disease, but not normal human τ. We synthesized tetradeka peptides corresponding to the original bovine sequence, its serine → proline substituted analog, the genuine human sequence of this region, and the bovine epitope phosphorylated on the crucial serene. The secondary structure of the peptides was determined by circular dichroism. It was found that only the original bovine epitope showed a tendency to form the (β-pleated sheets characteristic of the neurofibrillary tangles. The spectra of the human peptide, its analog, β and the phosphorylated bovine sequence were very similar, featuring a weak, helical β-turn character. Eventual phosphorylation of epitopes of this otherwise heavily phosphorylated protein may overcome inter-species conformational gaps.
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