Establishing the link between fibril formation and Raman optical activity spectra of insulin
Establishing the link between fibril formation and Raman optical activity spectra of insulin
复制标题
DOI：
10.1039/c7cp01556a
复制
发表时间：
2017-06-07
影响因子：
3.3
通讯作者：
Bour, Petr
中科院分区：
文献类型：
--
作者：
Kessler, Jiri;Yamamoto, Shigeki;Bour, Petr
蛋白质折叠成不溶性淀粉样原纤维涉及许多生物过程。光谱学是监测这种结构变化的便捷工具。最近，报道了胰岛素拉曼光学活性（ROA）光谱在前原纤维阶段的特征变化，但没有得到理论模型的支持。在本研究中，使用分子动力学和密度泛函理论来模拟光谱并了解结构、ROA 和拉曼光谱强度之间的联系。理论结果与观察结果一致，仅证实了 ROA 对蛋白质三级结构的异常敏感性。令人惊讶的是，这种敏感性反映了肽主链和侧链的局部构象变化，而不是蛋白质成分的直接空间相互作用。提供强 ROA 信号的侧链（例如酪氨酸）还可以报告局部构象特征。理论模型有助于解释观察到的光谱变化，并可能使 ROA 光谱在蛋白质结构研究中的未来应用成为可能。
Folding of proteins into insoluble amyloidal fibrils is implicated in a number of biological processes. Optical spectroscopy represents a convenient tool to monitor such structural variations. Recently, characteristic changes in Raman optical activity (ROA) spectra of insulin during a pre-fibrillar stage were reported but not supported by a theoretical model. In the present study, molecular dynamics and the density functional theory are used to simulate the spectra and understand the connection between the structure, and ROA and Raman spectral intensities. Theoretical results are consistent with the observations and only confirm exceptional ROA sensitivity to the protein tertiary structure. Surprisingly, this sensitivity reflects local conformational changes in the peptide main and side chains, rather than a direct through-space interaction of the protein components. Side chains providing strong ROA signals, such as tyrosine, can additionally report on local conformational features. Theoretical modeling helps in explaining the observed spectral changes and is likely to enable future applications of ROA spectroscopy in protein structural studies.