Structural Superimposition

Abstact

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-NH2 (L2) and Ac-KIIILK-NH2 (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.