Qiu Feng, Tang Chengkang, Chen Yongzhu
Laboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, 610041, China.
Core Facility of West China Hospital, Sichuan University, Chengdu, 610041, China.
J Pept Sci. 2018 Feb;24(2). doi: 10.1002/psc.3062. Epub 2017 Dec 14.
Amyloid-like aggregation of natural proteins or polypeptides is an important process involved in many human diseases as well as some normal biological functions. Plenty of works have been done on this ubiquitous phenomenon, but the molecular mechanism of amyloid-like aggregation has not been fully understood yet. In this study, we showed that a series of designer bolaamphiphilic peptides could undergo amyloid-like aggregation even though they didn't possess typical β-sheet secondary structure. Through systematic amino acid substitution, we found that for the self-assembling ability, the number and species of amino acid in hydrophobic section could be variable as long as enough hydrophobic interaction is provided, while different polar amino acids as the hydrophilic heads could change the self-assembling nanostructures with their aggregating behaviors affected by pH value change. Based on these results, novel self-assembling models and aggregating mechanisms were proposed, which might provide new insight into the molecular basis of amyloid-like aggregation.
天然蛋白质或多肽的淀粉样聚集是一个涉及许多人类疾病以及一些正常生物学功能的重要过程。针对这一普遍存在的现象已经开展了大量研究工作，但是淀粉样聚集的分子机制尚未完全明确。在本研究中，我们发现一系列人工合成的双亲性肽即便不具备典型的β-折叠二级结构，也能够发生淀粉样聚集。通过系统的氨基酸替换，我们发现对于自组装能力而言，疏水区域氨基酸的数量和种类可以有所不同，只要能提供足够的疏水相互作用即可，而作为亲水头部的不同极性氨基酸能够改变自组装纳米结构，其聚集行为受pH值变化的影响。基于这些结果，我们提出了新的自组装模型和聚集机制，这可能为淀粉样聚集的分子基础提供新的见解。
