CD and Solid-State NMR Studies of Low-Order Oligomers of Transthyretin.
CD and Solid-State NMR Studies of Low-Order Oligomers of Transthyretin.
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DOI：
10.1007/978-1-0716-2597-2_21
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发表时间：
2023
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表征在错误折叠和聚集的早期阶段填充的低聚中间状态对于理解致病蛋白质聚集的分子机制是必不可少的。越来越多的证据也表明，寡聚物种比成熟的纤维状物种毒性更大。在这里，我们描述了分离一种易于聚集的蛋白质的寡聚体种类，转甲状腺激素，与蛋白质错误折叠障碍有关，包括心肌病和多发性神经病。我们还描述了使用圆二色谱和固体核磁共振光谱研究低聚物物种结构的方法。这些方法也可应用于其他易聚集蛋白质的寡聚中间体的结构表征。
Characterization of oligomeric intermediate states populated at an early stage of misfolding and aggregation is essential to understanding molecular mechanism of pathogenic protein aggregation. Growing evidence also suggests that oligomeric species are more toxic than mature fibrillar counterparts. Here, we describe procedures for isolating oligomeric species of an aggregation-prone protein, transthyretin, associated with protein misfolding disorders, including cardiomyopathy and polyneuropathy. We also describe methods for structural studies of the oligomeric species using circular dichroism and solid-state NMR spectroscopy. These methods can be applied to structural characterization of oligomeric intermediates of other aggregation-prone proteins.