Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, Odisha 769008, India.
J Pept Sci. 2013 Sep;19(9):529-36. doi: 10.1002/psc.2539. Epub 2013 Jul 19.
The transformation of polypeptide chains from their globular native structure to fibrillar aggregates has been a matter of great concern because of the involvement of these aggregates in the onset of several degenerative diseases. These aggregates exhibit highly ordered cross β sheet structures and are known as 'amyloids'. Formation of amyloids in the body is associated with cytotoxicity due to direct interaction of the aggregated species with the cell membrane leading to cellular permeability or due to loss of functionality of the proteins involved in the amyloid formation. The preference of polypeptide chains to remain in their native conformation or to aggregate into amyloids is guided by several factors such as its conformation at specific condition, concentration, physicochemical properties of the amino acid sequence and so on. In the current review, we have reviewed the different factors that guide the transition of proteins from their natively folded state to the amyloidogenic state. Understanding the critical determinants of amyloidogenesis is vital towards deciphering the molecular mechanism of amyloidogenesis and for the development of effective therapeutics against amyloidosis.
多肽链从其球状天然结构向纤维状聚集物的转变一直是人们非常关注的问题，因为这些聚集物与多种退行性疾病的发生有关。这些聚集物表现出高度有序的交叉 β 片层结构，被称为“淀粉样蛋白”。由于聚集态物质与细胞膜的直接相互作用导致细胞通透性，或者由于参与淀粉样形成的蛋白质的功能丧失，体内淀粉样蛋白的形成与细胞毒性有关。多肽链保持其天然构象或聚集形成淀粉样蛋白的偏好受到多种因素的指导，例如其在特定条件下的构象、浓度、氨基酸序列的物理化学性质等。在本综述中，我们回顾了指导蛋白质从天然折叠状态向淀粉样变性状态转变的不同因素。理解淀粉样蛋白形成的关键决定因素对于揭示淀粉样蛋白形成的分子机制以及开发针对淀粉样变性的有效治疗方法至关重要。
