Nanoscale Structural Analysis of a Lipid-Driven Aggregation of Insulin.

Nanoscale Structural Analysis of a Lipid-Driven Aggregation of Insulin.
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脂质驱动的胰岛素聚集的纳米级结构分析。

DOI:
10.1021/acs.jpclett.1c04012
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发表时间:
2022-03-17
影响因子:
5.7
通讯作者:
Kurouski, Dmitry
Kurouski, Dmitry
中科院分区:
化学2区
文献类型:
--
作者:
Rizevsky, Stanislav;Matveyenka, Mikhail;Kurouski, Dmitry

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错误折叠蛋白质的突然聚集是大量严重病理的标志,包括1型和2型糖尿病、阿尔茨海默病和帕金森病。越来越多的证据表明,脂质可以独特地改变淀粉样蛋白相关蛋白的速率,以及改变形成的低聚物和原纤维的结构。在这项研究中,我们利用原子力显微镜红外(AFM-IR)光谱,也被称为纳米红外光谱,检查个人的胰岛素低聚物,原丝和原纤维的结构中生长的磷脂。我们的研究结果表明,胰岛素低聚物的AFM-IR光谱具有强烈的C-H和PO 2 −振动信号,这表明低聚物结构中存在脂质。此外,已观察到的低聚物的AFM-IR光谱中的脂质振动相对于纯脂质的相应频带的实质性位移。这表明在寡聚体形成阶段形成的脂质和蛋白质之间存在强烈的相互作用。
Abrupt aggregation of misfolded proteins is a hallmark of a large number of severe pathologies, including diabetes types 1 and 2, Alzheimer, and Parkinson diseases. A growing body of evidence suggests that lipids can uniquely change rates of amyloid-associated proteins as well as modify the structure of formed oligomers and fibrils. In this study, we utilize atomic force microscopy infrared (AFM-IR) spectroscopy, also known as nano-IR spectroscopy, to examine the structure of individual insulin oligomers, protofilaments, and fibrils grown in the presence of phospholipids. Our findings show that AFM-IR spectra of insulin oligomers have strong signals of C–H and PO2− vibrations, which points on the presence of lipids in the oligomer structure. Furthermore, substantial shifts in lipid vibrations in AFM-IR spectra of the oligomers relative to the corresponding bands of pure lipids have been observed. This points on strong interactions between a lipid and a protein that are developed at the stage of the oligomer formation.
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