人工设计GAV-6短肽自组装形成淀粉样纤维的研究

Study on the Formation of Amyloid Fibrils by Self-assembly of an Artificially Designed Peptide GAV-6

淀粉样纤维是一类与人类疾病密切相关的蛋白异常聚集体,从一些核心短肽序列入手研究天然蛋白形成淀粉样纤维的分子机制是近年来的研究热点。本文设计了一个由甘氨酸(G)、丙氨酸(A)、缬氨酸(V)三种疏水性氨基酸构成的六肽GGAAVV(GAV-6),并研究其形成淀粉样纤维的能力。以原子力显微镜(AFM)和动态光散射(DLS)为手段的纳米结构表征发现,GAV-6能够在水溶液中自组装形成光滑不分叉的纳米纤维。通过刚果红染色/结合实验和硫磺素T结合实验,我们证实了这些纳米纤维具有典型的淀粉样纤维的特征。上述结果表明,人工设计的GAV-6短肽能够自组装形成淀粉样纤维,这可能为今后深入研究天然蛋白形成淀粉样纤维的机制提供一种简单的模式分子。

Amyloid fibrils belong to a category of abnormal aggregations of natural proteins, which are closely related to many human diseases. Recently, some critical peptide sequences have been extensively studied for clarifying the molecular mechanism of natural proteins to form amyloid fibrils. In the present study, we designed a short peptide GGAAVV （GAV-6） composed of hydrophobic amino acids glycine （G）, alanine （A） and valine （V） and studied its ability to form amyloid fibrils. As characterized by atomic force microscopy （AFM） and dynamic light scattering （DLS）, the peptide could self-assemble into smooth nanofibers without branches. Congo red staining/binding and thioflavin-T （ThT） binding experiments show that the nanofibers formed by GAV 6 shared identical properties with typical amyloid fibrils. These results show that the designed peptide GAV-6 could self-assemble into typical amyloid fibrils, which might make it a useful model molecule to clarify the mechanism for the formation of amyloid fibrils in the future.