Zn2+ 结合通过破坏反平行结构中的盐桥来增加Aβ(16-22) 寡头中的平行结构
Yongshun Song1, Mengjiao Wu1, Changying Wang2
1School of Physics, East China University of Science and Technology, Shanghai 200237, China.
The journal of physical chemistry. B
|January 31, 2024
概括
粉样β (Aβ) 自组合成有毒聚合物是阿尔茨海默病的关键. 这项研究揭示了Zn2+破坏了Aβ16−22反平行结构,有利于混合形式,并提供了对聚合中的金属离子作用的见解.
科学领域:
- 生物化学 生化学
- 计算生物学 计算生物学
- 神经科学是一个神经科学.
背景情况:
- 粉样β (Aβ) 聚合成寡聚体和斑块是阿尔茨海默氏症病原体的核心.
- 疏水性Aβ16−22核心对于全长Aβ纤维化至关重要.
- 早期的Aβ聚合物表现出多样化的β片结构,与晚期的同质反平行安排不同.
研究的目的:
- 为了研究Aβ16−22的自我组装结构.
- 为了确定Zn2+对Aβ16−22聚合物的结构概率的影响.
- 阐明金属离子在短的自组合中的作用.
主要方法:
- 复制品交换分子动力学模拟被使用.
- 分析的重点是Aβ16−22.22的各种自我组装结构的出现概率.
- 专门研究了Zn2+对这些结构概率的影响.
主要成果:
- 在水中,Aβ16−22很容易形成β叶结构,其中反平行安排占主导地位 (24.8%的trimers).
- 通过破坏Lys16-Glu22盐桥,添加Zn2+显著降低了反平行三元体结构 (至12.5%).
- 存在Zn2+增加了混合反平行/平行结构的可能性.
结论:
- 在Aβ16−22寡合体中,反平行和平行排列之间存在结构竞争.
- Zn2+ 离子调节 Aβ16−22 寡合体结构,影响聚合途径.
- 金属离子在短粉样蛋白的自我组装动态中起着重要作用.
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