Bemporad Francesco, Chiti Fabrizio
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Chem Biol. 2012 Mar 23;19(3):315-27. doi: 10.1016/j.chembiol.2012.02.003.
The conversion of proteins from their native state to misfolded oligomers is associated with, and thought to be the cause of, a number of human diseases, including Alzheimer's disease, Parkinson's disease, and systemic amyloidoses. The study of the structure, mechanism of formation, and biological activity of protein misfolded oligomers has been challenged by the metastability, transient formation, and structural heterogeneity of such species. In spite of these difficulties, in the past few years, many experimental approaches have emerged that enable the detection and the detailed molecular study of misfolded oligomers. In this review, we describe the basic and generic knowledge achieved on protein oligomers, describing the mechanisms of oligomer formation, the methodologies used thus far for their structural determination, and the structural elements responsible for their toxicity.
蛋白质从天然状态转变为错误折叠的寡聚体与许多人类疾病相关，并且被认为是这些疾病的病因，包括阿尔茨海默病、帕金森病和系统性淀粉样变性。蛋白质错误折叠寡聚体的结构、形成机制和生物活性的研究一直受到这些物种的亚稳定性、瞬时形成和结构异质性的挑战。尽管存在这些困难，但在过去几年中，出现了许多实验方法，能够对错误折叠的寡聚体进行检测和详细的分子研究。在本综述中，我们描述了在蛋白质寡聚体方面取得的基本和通用知识，阐述了寡聚体形成的机制、迄今为止用于其结构测定的方法以及导致其毒性的结构元件。
