School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences , Tel Aviv University , Ramat Aviv 69978 , Israel.
Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics , Nanjing University , Nanjing , Jiangsu 210093 , People's Republic of China.
ACS Nano. 2020 Feb 25;14(2):1694-1706. doi: 10.1021/acsnano.9b07307. Epub 2020 Jan 21.
Most natural biomolecules may exist in either of two enantiomeric forms. Although in nature, amino acid biopolymers are characterized by l-type homochirality, incorporation of d-amino acids in the design of self-assembling peptide motifs has been shown to significantly alter enzyme stability, conformation, self-assembly behavior, cytotoxicity, and even therapeutic activity. However, while functional metabolite assemblies are ubiquitous throughout nature and play numerous important roles including physiological, structural, or catalytic functions, the effect of chirality on the self-assembly nature and function of single amino acids is not yet explored. Herein, we investigated the self-assembly mechanism of amyloid-like structure formation by two aromatic amino acids, phenylalanine (Phe) and tryptophan (Trp), both previously found as extremely important for the nucleation and self-assembly of aggregation-prone peptide regions into functional structures. Employing d-enantiomers, we demonstrate the critical role that amino acid chirality plays in their self-assembly process. The kinetics and morphology of pure enantiomers is completely altered upon their coassembly, allowing to fabricate different nanostructures that are mechanically more robust. Using diverse experimental techniques, we reveal the different molecular arrangement and self-assembly mechanism of the dl-racemic mixtures that resulted in the formation of advanced supramolecular materials. This study provides a simple yet sophisticated engineering model for the fabrication of attractive materials with bionanotechnological applications.
大多数天然生物分子可能以两种对映异构体中的任意一种存在。虽然在自然界中，氨基酸生物聚合物的特征是 l 型手性同型性，但在自组装肽基序的设计中加入 d-氨基酸已被证明会显著改变酶的稳定性、构象、自组装行为、细胞毒性，甚至治疗活性。然而，虽然功能代谢物组装在自然界中无处不在，并发挥着许多重要作用，包括生理、结构或催化功能，但手性对单个氨基酸自组装性质和功能的影响尚未得到探索。在这里，我们研究了两种芳香族氨基酸，苯丙氨酸（Phe）和色氨酸（Trp），通过它们的自组装机制来形成淀粉样结构。这两种氨基酸以前都被发现对聚集倾向肽区域形成功能结构的成核和自组装非常重要。使用 d-对映异构体，我们证明了氨基酸手性在它们的自组装过程中起着关键作用。纯对映异构体的动力学和形态完全改变，当它们共组装时，允许制造出更坚固的不同纳米结构。使用多种实验技术，我们揭示了 dl-外消旋混合物的不同分子排列和自组装机制，导致了先进的超分子材料的形成。这项研究为制造具有生物纳米技术应用吸引力的材料提供了一个简单而复杂的工程模型。
