Binary Structure of Amyloid Beta Oligomers Revealed by Dual Recognition Mapping.
Binary Structure of Amyloid Beta Oligomers Revealed by Dual Recognition Mapping.
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DOI：
10.1021/acs.analchem.9b01316
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发表时间：
2019-05
影响因子：
7.4
通讯作者：
Jihyun Yoon;Youngkyu Kim;Joon Won Park
中科院分区：
文献类型：
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作者：
Jihyun Yoon;Youngkyu Kim;Joon Won Park
β淀粉样蛋白（Aβ）寡聚体被广泛认为是阿尔茨海默病（AD）的病原体，AD是一种进行性神经退行性疾病。因此，确定寡聚体的结构对于理解疾病和开发治疗剂是重要的;然而，由于异质性、非结晶性和可变性，阐明结构已被证明是困难的。在此，我们使用原子力显微镜（AFM）研究了Aβ40和Aβ42的同源和异源寡聚体，并揭示了分子结构的特征。通过检查单个寡聚体的表面与顺序的N-和C-末端特异性抗体栓系的提示，我们同时映射的N-和C-末端分布和弹性模量。有趣的是，Aβ肽的N-和C-末端在寡聚体表面上都被识别，并且末端检测的像素区域表现出比沉默像素区域更低的弹性模量。这两种类型的区域随机分布在低聚物表面上。
Amyloid beta (Aβ) oligomers are widely considered to be the causative agent of Alzheimer's disease (AD), a progressive neurodegenerative disorder. Determining the structure of oligomers is, therefore, important for understanding the disease and developing therapeutic agents; however, elucidating the structure has been proven difficult due to heterogeneity, noncrystallinity, and variability. Herein, we investigated homo- and hetero-oligomers of Aβ40 and Aβ42 using atomic force microscopy (AFM) and revealed characteristics of the molecular structure. By examining the surface of individual oligomers with sequential N- and C-terminus specific antibody-tethered tips, we simultaneously mapped the N- and C-terminus distributions and the elastic modulus. Interestingly, both the N- and C-termini of Aβ peptides were recognized on the oligomer surface, and the termini detected pixel regions exhibited a lower elastic modulus than silent pixel regions. These two types of regions were randomly distributed on the oligomer surface.