The relationship between amyloid structure and cytotoxicity.
The relationship between amyloid structure and cytotoxicity.
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作者：
Marshall KE;Marchante R;Xue WF;Serpell LC
蛋白质和肽自组装成淀粉样蛋白结构一直是密集和集中研究的主题，因为它们与人类和哺乳动物中的神经变性、年龄相关的人类疾病和传染性朊病毒疾病有关。在疾病相关的淀粉样蛋白组装体中，从小的寡聚组装体中间体到纤维状结构的各种种类已被证明具有潜在毒性。同样，已经发现由相同疾病相关淀粉样蛋白序列形成的一系列物种在相当的单体当量浓度和条件下是相对良性的。近年来，越来越多的功能性淀粉样蛋白系统也被发现，这些进展表明，并非所有的淀粉样蛋白结构都对细胞具有毒性。鉴于这些观察结果，重要的是要了解为什么淀粉样蛋白结构可能编码这种不同的毒性潜力，尽管共享一个共同的核心分子结构。在这里，我们讨论了淀粉样蛋白的结构和组装机制与其不同的功能效应的不同方面之间可能存在的联系。我们提出了淀粉样蛋白结构和其毒性潜力之间的关系的背景下，淀粉样蛋白的序列，结构和毒性关系的最新报告可验证的假设。
Self-assembly of proteins and peptides into amyloid structures has been the subject of intense and focused research due to their association with neurodegenerative, age-related human diseases and transmissible prion diseases in humans and mammals. Of the disease associated amyloid assemblies, a diverse array of species, ranging from small oligomeric assembly intermediates to fibrillar structures, have been shown to have toxic potential. Equally, a range of species formed by the same disease associated amyloid sequences have been found to be relatively benign under comparable monomer equivalent concentrations and conditions. In recent years, an increasing number of functional amyloid systems have also been found. These developments show that not all amyloid structures are generically toxic to cells. Given these observations, it is important to understand why amyloid structures may encode such varied toxic potential despite sharing a common core molecular architecture. Here, we discuss possible links between different aspects of amyloidogenic structures and assembly mechanisms with their varied functional effects. We propose testable hypotheses for the relationship between amyloid structure and its toxic potential in the context of recent reports on amyloid sequence, structure, and toxicity relationships.