Heterogeneous Amyloid β-Sheet Polymorphs Identified on Hydrogen Bond Promoting Surfaces Using 2D SFG Spectroscopy
Heterogeneous Amyloid β-Sheet Polymorphs Identified on Hydrogen Bond Promoting Surfaces Using 2D SFG Spectroscopy
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DOI：
10.1021/acs.jpca.7b11934
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发表时间：
2018-02-08
影响因子：
2.9
通讯作者：
Zanni, Martin T.
中科院分区：
文献类型：
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作者：
Ho, Jia-Jung;Ghosh, Ayanjeet;Zanni, Martin T.
利用二维和频产生光谱（2D SFG）研究了五肽FGAIL在氢键促进表面上的结构。FGAIL是人类胰岛淀粉样多肽（hIAPP或amylin）中最易发生淀粉样蛋白的部分。在纯金表面存在时，FGAIL不会形成有序结构。当金被自组装的巯基苯甲酸单层（MBA）涂层时，二维SFG光谱显示了与β -薄片相关的特征。还观察到FGAIL肽和MBA单层羧酸基团之间的交叉峰，表明肽与表面头基密切接触。在第二组样品中，化学连接到MBA单层的FGAIL肽也表现出β -sheet特征，但光谱要简单得多。通过模拟实验，我们得出结论，氢键促进表面催化形成具有不同取向的平行和反平行β -片结构。当结扎时，只有单一方向的平行薄片是主要结构。因此，这种促进氢键的表面产生了异质分布的多晶结构，与允许许多不同淀粉样蛋白种子结构成核的浓度效应相一致。一个定义明确的种子有利于一种多晶型而不是其他多晶型，这表明膜的集中影响可以被有利于定向纤维生长的因素抵消。这些实验为外差探测二维SFG光谱测量和解释β -片结构奠定了基础。该模型系统的结果表明，在自然界中发现的多态分布的异质性表明非选择性淀粉样蛋白聚集，而多态结构的狭窄分布与指导纤维生长的特定蛋白质或脂质相互作用一致。
Two-dimensional sum-frequency generation spectroscopy (2D SFG) is used to study the structures of the pentapeptide FGAIL on hydrogen bond promoting surfaces. FGAIL is the most amyloidogenic portion of the human islet amyloid polypeptide (hIAPP or amylin). In the presence of a pure gold surface, FGAIL does not form ordered structures. When the gold is coated with a self-assembled monolayer of mercaptobenzoic acid (MBA), 2D SFG spectra reveal features associated with beta-sheets. Also observed are cross peaks between the FGAIL peptides and the carboxylic acid groups of the MBA monolayer, indicating that the peptides are in close contact with the surface headgroups. In the second set of samples, FGAIL peptides chemically ligated to the MBA monolayer also exhibited beta-sheet features but with a much simpler spectrum. From simulations of the experiments, we conclude that the hydrogen bond promoting surface catalyzes the formation of both parallel and antiparallel beta-sheet structures with several different orientations. When ligated, parallel sheets with only a single orientation are the primary structure. Thus, this hydrogen bond promoting surface creates a heterogeneous distribution of polymorph structures, consistent with a concentration effect that allows nucleation of many different amyloid seeding structures. A single well-defined seed favors one polymorph over the others, showing that the concentrating influence of a membrane can be counterbalanced by factors that favor directed fiber growth. These experiments lay the foundation for the measurement and interpretation of beta-sheet structures with heterodyne detected 2D SFG spectroscopy. The results of this model system suggest that a heterogeneous distribution of polymorphs found in nature are an indication of nonselective amyloid aggregation whereas a narrow distribution of polymorph structures is consistent with a specific protein or lipid interaction that directs fiber growth.