Ledesma M D, Bonay P, Avila J
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
J Neurochem. 1995 Oct;65(4):1658-64. doi: 10.1046/j.1471-4159.1995.65041658.x.
Glycated residues of tau protein from paired helical filaments isolated from the brains of Alzheimer's disease patients were localized by doing a proteolytic cleavage of the protein, fractionation of the resulting peptides, and identification of those peptides using specific antibodies. The most suitable residues for glycation, lysines, present at the tubulin-binding motif of tau protein, seem to be preferentially modified compared with those lysines present at other regions. Among these modified lysines, those located in the sequence comprising residues 318-336 (in the largest human tau isoform) were found to be glycated, as determined by the reaction with an antibody that recognizes a glycated peptide containing this sequence. Because those lysines are present in a tubulin binding motif of tau protein, its modification could result in a decrease in the interaction of tau with tubulin.
通过对蛋白质进行蛋白水解切割、对所得肽段进行分级分离并使用特异性抗体鉴定这些肽段，确定了从阿尔茨海默病患者大脑中分离出的成对螺旋丝中tau蛋白的糖化残基。与存在于tau蛋白其他区域的赖氨酸相比，tau蛋白微管蛋白结合基序处存在的最适合糖化的残基（赖氨酸）似乎优先被修饰。在这些修饰的赖氨酸中，通过与识别包含该序列的糖化肽段的抗体反应确定，位于包含318-336位残基的序列（在最大的人类tau异构体中）中的赖氨酸被糖化。由于这些赖氨酸存在于tau蛋白的微管蛋白结合基序中，其修饰可能导致tau与微管蛋白的相互作用减少。
