多重扩张揭示了在健康和患病的大脑中成像多蛋白质纳米结构
Jinyoung Kang1,2, Margaret E Schroeder1,3, Youngmi Lee1
1McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
Nature communications
|November 9, 2024
概括
多重扩展揭示 (multiExR) 允许同时对20多种蛋白质进行高保真可视化. 这种技术精确地绘制了生物样本中的蛋白质组织,有助于疾病研究.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 蛋白质形成纳米结构,在生理和疾病状态中至关重要.
- 现有的蛋白质可视化方法在复合和纳米尺度成像方面存在局限性.
- 扩展揭示 (ExR) 以前是为了改善抗体标记和纳米尺度成像而开发的.
研究的目的:
- 引入多重扩展揭示 (multiExR) 来实现单个样本中多个蛋白质的高保真可视化.
- 评估生物样本中多ExR的注册准确性和实用性.
主要方法:
- 多ExR协议涉及连续轮抗体染色和成像.
- 对圆对圆和整体注册错误的定量分析.
- 在阿尔茨海默病的小鼠大脑模型和初级体感皮质中应用multiExR来绘制蛋白质组织图.
主要成果:
- 通过MultiExR,可以在同一样本中高于20种蛋白质的高保真抗体可视化.
- 在严格条件下,中位数注册误差为39nm,在严格条件下为25nm.
- 精确地绘制了阿尔茨海默病模型小鼠大脑中的23种蛋白质,揭示了减少的突触蛋白质集群体体积和与β-粉样蛋白的同定位.
- 在小鼠初级体感皮质中可视化了20个突触蛋白.
结论:
- MultiExR显著提升了可视化和分析纳米级蛋白质组织的能力.
- 这种技术为正常生物过程和疾病状态中的蛋白质相互作用提供了宝贵的见解.
- MultiExR是一种广泛适用的工具,用于研究复杂的蛋白质纳米结构.
相关概念视频
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:33Proteomics
A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term proteomics...
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term proteomics...