Abstract

Zinc ions and glycosaminoglycans (GAGs) are found in amyloid deposits and are known to modulate the β-amyloid peptide (Аβ) aggregation, which is thought to be a key event in the pathogenesis of Alzheimer’s disease (AD). Correlation spectroscopy was used to study how the H6R and D7H mutations of the metal-binding domain (MBD) of Аβ42 affect the modulation of its zinc-induced aggregation by the model GAG heparin. The H6R mutation was shown to decrease and the D7H mutation to increase the Аβ42 propensity to aggregate in the presence of zinc ions. In addition, H6R diminished and D7H enhanced the modulating effect of heparin. The difference in the heparin-dependent modulation was associated with coordination of zinc ions within the MBDs of the mutant peptides. The findings indicate that anion-binding sites formed by complexes of zinc ions with the Аβ MBD play an essential role in the interaction of zinc-induced Аβ aggregates with heparin.

中文翻译：

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H6R和D7H突变对锌诱导的淀粉样β聚集体肝素依赖性调节的影响。

摘要

锌离子和糖胺聚糖（GAG）存在于淀粉样蛋白沉积物中，并已知可调节β淀粉样肽（Аβ）的聚集，这被认为是阿尔茨海默氏病（AD）发病机理中的关键事件。相关光谱法用于研究模型GAG肝素对Аβ42的金属结合域（MBD）的H6R和D7H突变如何影响其锌诱导的聚集的调节。在锌离子存在下，H6R突变减少，而D7H突变增加Аβ42聚集的倾向。此外，H6R减少，D7H增强肝素的调节作用。肝素依赖性调节的差异与突变肽的MBD内锌离子的配位有关。