New Insights from Sum Frequency Generation Vibrational Spectroscopy into the Interactions of Islet Amyloid Polypeptides with Lipid Membranes.
New Insights from Sum Frequency Generation Vibrational Spectroscopy into the Interactions of Islet Amyloid Polypeptides with Lipid Membranes.
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DOI：
10.1155/2016/7293063
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发表时间：
2016
影响因子：
4.3
通讯作者：
Yan EC
中科院分区：
文献类型：
--
作者：
Fu L;Wang Z;Batista VS;Yan EC
近年来，膜表面淀粉样多肽的研究受到越来越多的关注。多项研究表明，膜可以催化蛋白质聚集，淀粉样蛋白聚集的早期产物可以破坏膜的完整性，增加水的渗透性并诱导离子细胞毒性。尽管如此，探测淀粉样蛋白在膜表面的聚集具有挑战性。需要表面特异性方法来区分膜界面处聚集体与体相中聚集体的贡献，并在不使用扰动光谱标签的情况下原位实时表征蛋白质二级结构。在这里，我们回顾了和频发生（SFG）振动光谱与计算建模技术相结合的最新应用，这是一种联合实验和计算方法，为膜表面胰岛淀粉样多肽（IAPP）的聚集提供了有价值的见解。这些应用表明，SFG 可以提供有关 IAPP 在界面聚集过程中的结构、动力学和方向的详细信息，与 II 型糖尿病的分子机制相关。这些最新进展证明了 SFG 作为在分子水平上研究淀粉样蛋白疾病和针对膜表面早期聚集产物的合理药物设计的新方法的前景。
Studies of amyloid polypeptides on membrane surfaces have gained increasing attention in recent years. Several studies have revealed that membranes can catalyze protein aggregation and that the early products of amyloid aggregation can disrupt membrane integrity, increasing water permeability and inducing ion cytotoxicity. Nonetheless, probing aggregation of amyloid proteins on membrane surfaces is challenging. Surface-specific methods are required to discriminate contributions of aggregates at the membrane interface from those in the bulk phase and to characterize protein secondary structures in situ and in real time without the use of perturbing spectroscopic labels. Here, we review the most recent applications of sum frequency generation (SFG) vibrational spectroscopy applied in conjunction with computational modeling techniques, a joint experimental and computational methodology that has provided valuable insights into the aggregation of islet amyloid polypeptide (IAPP) on membrane surfaces. These applications show that SFG can provide detailed information about structures, kinetics, and orientation of IAPP during interfacial aggregation, relevant to the molecular mechanisms of type II diabetes. These recent advances demonstrate the promise of SFG as a new approach for studying amyloid diseases at the molecular level and for the rational drug design targeting early aggregation products on membrane surfaces.