Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
Biochem Biophys Res Commun. 2010 May 21;396(1):2-6. doi: 10.1016/j.bbrc.2010.02.105.
Amyloid consists of cross-beta-sheet fibrils and is associated with about 25 human diseases, including several neurodegenerative diseases, systemic and localized amyloidoses and type II diabetes mellitus. Amyloid-forming proteins differ in structures and sequences, and it is to a large extent unknown what makes them convert from their native conformations into amyloid. In this review, current understanding of amino acid sequence determinants and the effects of molecular chaperones on amyloid formation are discussed. Studies of the nonpolar, transmembrane surfactant protein C (SP-C) have revealed amino acid sequence features that determine its amyloid fibril formation, features that are also found in the amyloid beta-peptide in Alzheimer's disease and the prion protein. Moreover, a proprotein chaperone domain (CTC(Brichos)) that prevents amyloid-like aggregation during proSP-C biosynthesis can prevent fibril formation also of other amyloidogenic proteins.
淀粉样蛋白由交叉β-折叠纤维组成，与约 25 种人类疾病有关，包括几种神经退行性疾病、系统性和局部淀粉样变性以及 2 型糖尿病。淀粉样蛋白形成蛋白在结构和序列上存在差异，很大程度上不清楚是什么导致它们从天然构象转化为淀粉样蛋白。在这篇综述中，讨论了当前对氨基酸序列决定因素以及分子伴侣对淀粉样蛋白形成的影响的理解。对非极性、跨膜表面活性剂蛋白 C（SP-C）的研究揭示了决定其淀粉样纤维形成的氨基酸序列特征，这些特征也存在于阿尔茨海默病中的β-淀粉样肽和朊病毒蛋白中。此外，一个前蛋白伴侣结构域（CTC（Brichos））可以防止前 SP-C 生物合成过程中类似淀粉样的聚集，也可以防止其他淀粉样蛋白形成纤维。
