Ordered Packing of β-Sheet Nanofibrils into Nanotubes: Multi-hierarchical Assembly of Designed Short Peptides
Xiaoyue Ma, Yurong Zhao, Chunyong He, Xing Zhou, Hao Qi, Yan Wang, Cuixia Chen, Dong Wang, Jie Li, Yubin Ke, Jiqian Wang, Hai Xu
Abstract
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-I3GGHK-NH2 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-I3GGGK-NH2, Ac-I3GGFK-NH2, and Ac-I3GGDHDK-NH2 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.