Das Abhinaba, Gnewou Ordy, Zuo Xiaobing, Wang Fengbin, Conticello Vincent P
Department of Chemistry, Emory University, Atlanta, GA, 30322, USA.
X-ray Science Division, Argonne National Laboratory, Lemont, IL, 60439, USA.
Faraday Discuss. 2025 May 16. doi: 10.1039/d4fd00190g.
Surfactant-like peptides, in which hydrophilic and hydrophobic residues are encoded within different domains in the peptide sequence, undergo facile self-assembly in aqueous solution to form supramolecular hydrogels. These peptides have been explored extensively as substrates for the creation of functional materials since a wide variety of amphipathic sequences can be prepared from commonly available amino acid precursors. The self-assembly behavior of surfactant-like peptides has been compared to that observed for small molecule amphiphiles in which nanoscale phase separation of the hydrophobic domains drives the self-assembly of supramolecular structures. Here, we investigate the relationship between sequence and supramolecular structure for a pair of bola-amphiphilic peptides, Ac-KLIIIK-NH (L2) and Ac-KIIILK-NH (L5). Despite similar length, composition, and polar sequence pattern, L2 and L5 form morphologically distinct assemblies, nanosheets and nanotubes, respectively. Cryo-EM helical reconstruction was employed to determine the structure of the L5 nanotube at near-atomic resolution. Rather than displaying self-assembly behavior analogous to conventional amphiphiles, the packing arrangement of peptides in the L5 nanotube displayed steric zipper interfaces that resembled those observed in the structures of β-amyloid fibrils. Like amyloids, the supramolecular structures of the L2 and L5 assemblies were sensitive to conservative amino acid substitutions within an otherwise identical amphipathic sequence pattern. This study highlights the need to better understand the relationship between sequence and supramolecular structure to facilitate the development of functional peptide-based materials for biomaterials applications.
类表面活性剂肽的亲水性和疏水性残基编码在肽序列的不同结构域中，在水溶液中易于自组装形成超分子水凝胶。由于可以从常用的氨基酸前体制备多种两亲性序列，这些肽已被广泛探索作为制备功能材料的底物。类表面活性剂肽的自组装行为已与小分子两亲物的自组装行为进行了比较，小分子两亲物中疏水结构域的纳米级相分离驱动超分子结构的自组装。在此，我们研究了一对双性离子两亲肽Ac-KLIIIK-NH（L2）和Ac-KIIILK-NH（L5）的序列与超分子结构之间的关系。尽管L2和L5的长度、组成和极性序列模式相似，但它们分别形成了形态不同的组装体，即纳米片和纳米管。采用冷冻电镜螺旋重建技术在近原子分辨率下确定了L5纳米管的结构。L5纳米管中肽的堆积排列并非表现出与传统两亲物类似的自组装行为，而是显示出类似于在β-淀粉样纤维结构中观察到的空间拉链界面。与淀粉样蛋白一样，L2和L5组装体的超分子结构对在其他方面相同的两亲性序列模式内的保守氨基酸取代敏感。这项研究强调了需要更好地理解序列与超分子结构之间的关系，以促进用于生物材料应用的基于肽的功能材料的开发。
