Marshall Karen E, Serpell Louise C
Department of Chemistry and Biochemistry, School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
Biochem Soc Trans. 2009 Aug;37(Pt 4):671-6. doi: 10.1042/BST0370671.
The folding of a protein from a sequence of amino acids to a well-defined tertiary structure is one of the most studied and enigmatic events to take place in biological systems. Relatively recently, it has been established that some proteins and peptides are able to take on conformations other than their native fold to form long fibres known as amyloid. In vivo, these are associated with misfolding diseases, such as Alzheimer's disease, Type 2 diabetes and the amyloidoses. In vitro, peptide assembly leads to amyloid-like fibres that have high stability, resistance to degradation and high tensile strength. Remarkably, despite the lack of any obvious sequence similarity between these fibrillogenic proteins and peptides, all amyloid fibrils share common structural characteristics and their underlying structure is known as 'cross-beta'. Nature is rich in beta-sheet protein assemblies such as spider silk and other 'useful' amyloids such as curli from Escherichia coli, where the strength of fibrils is fundamental to their function.
蛋白质从氨基酸序列折叠成明确的三级结构是生物系统中研究最多且最神秘的事件之一。直到最近,人们才确定一些蛋白质和肽能够呈现出与其天然折叠不同的构象,形成称为淀粉样蛋白的长纤维。在体内,这些与错误折叠疾病有关,如阿尔茨海默病、2型糖尿病和淀粉样变性。在体外,肽组装会形成具有高稳定性、抗降解性和高拉伸强度的淀粉样纤维。值得注意的是,尽管这些成纤维蛋白和肽之间缺乏任何明显的序列相似性,但所有淀粉样纤维都具有共同的结构特征,其基础结构被称为“交叉β”。自然界富含β-折叠蛋白组装体,如蜘蛛丝,以及其他“有用的”淀粉样蛋白,如大肠杆菌的卷曲菌毛,其中纤维的强度对其功能至关重要。