铜结合改变了由Y145Stop人类蛋白形成的粉样纤维的核心结构
Vidhyalakshmi Sridharan1, Tara George1, Daniel W Conroy1
1Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA. jaroniec.1@osu.edu.
Physical chemistry chemical physics : PCCP
|October 11, 2024
概括
铜与蛋白 (PrP) 的结合会影响其聚合成粉样纤维. 这项研究表明,结合的铜会诱导独特的纤维结构,模仿与疾病相关的突变,突出显示铜在子疾病中的作用.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 传染性海绵状脑病 (子疾病) 涉及错误折叠的子蛋白 (PrP) 聚合.
- 过渡金属离子,如铜,涉及PrP功能和疾病发病.
- 了解铜在PrP聚合中的作用对于子疾病研究至关重要.
研究的目的:
- 研究铜 (II) (Cu2+) 结合对人类蛋白 (huPrP) 聚合和纤维结构的影响.
- 阐明铜在huPrP中诱导的特定结合点和形状变化.
主要方法:
- 使用Y145Stop人类蛋白变体 (huPrP23-144) 作为模型系统.
- 采用多维解决方案和固态NMR光谱学.
- 应用原子力显微镜和硫黄素T光测试.
主要成果:
- Cu2+与huPrP23-144结合,产生了具有独特核心结构的粉样纤维.
- 这种Cu2+诱导的结构类似于与A117V突变相关的PrP株的结构.
- 铜与C终端结合的His残留物 (96,111,140) 似乎主要负责构造变化.
结论:
- 铜 (II) 结合显著改变 huPrP 纤维的结构,可能促进与疾病相关的菌株.
- 这些发现表明,铜离子在调节蛋白聚合通路方面发挥着直接作用.
- 准铜相互作用可能为子疾病提供新的治疗策略.
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