State Key Laboratory of Heavy Oil Processing and Center for Biotechnology and Bioengineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China.
Spallation Neutron Source Science Center, Dalang, Dongguan 523803, China.
Nano Lett. 2021 Dec 22;21(24):10199-10207. doi: 10.1021/acs.nanolett.1c02944. Epub 2021 Dec 6.
Although it is well-known proteins and their complexes are hierarchically organized and highly ordered structures, it remains a major challenge to replicate their hierarchical self-assembly process and to fabricate multihierarchical architectures with well-defined shapes and monodisperse characteristic sizes via peptide self-assembly. Here we describe an amphiphilic short peptide Ac-IGGHK-NH that first preassembles into thin, left-handed β-sheet nanofibrils, followed by their ordered packing into right-handed nanotubes. The key intermediate morphology and structures featuring the hierarchical process are simultaneously demonstrated. Further mechanistic exploration with the variants Ac-IGGGK-NH, Ac-IGGFK-NH, and Ac-IGGHK-NH reveals the vital role of multiple His-His side chain interactions between nanofibrils in mediating higher-order assembly and architectures. Altogether, our findings not only advance current understanding of hierarchical assembly of peptides and proteins but also afford a paradigm of how to take advantage of side chain interactions to construct higher-order assemblies with enhanced complexities.
尽管众所周知蛋白质及其复合物是具有层次结构和高度有序的结构，但通过肽自组装来复制其层次自组装过程并制造具有明确定义形状和单分散特征尺寸的多级结构仍然是一个主要挑战。在这里，我们描述了一种两亲性短肽 Ac-IGGHK-NH，它首先预组装成薄的左手β-片纳米纤维，然后有序地组装成右手纳米管。同时展示了关键的中间形态和具有层次过程的结构。进一步用变体 Ac-IGGGK-NH、Ac-IGGFK-NH 和 Ac-IGGHK-NH 进行的机制探索表明，纳米纤维之间的多个 His-His 侧链相互作用在介导高级组装和结构方面起着至关重要的作用。总的来说，我们的发现不仅推进了对肽和蛋白质的层次组装的现有理解，而且还提供了一个范例，说明如何利用侧链相互作用来构建具有增强复杂性的高级组装。
