SUMMARYThe self-assembly of designed peptides into filaments and other higher-order structures has been the focus of intense interest because of the potential for creating new biomaterials and biomedical devices. These peptide assemblies have also been used as models for understanding biological processes, such as the pathological formation of amyloid. We investigate the assembly of an octapeptide sequence, Ac-FKFEFKFE-NH 2 , motivated by prior studies that demonstrated that this amphipathic strand peptide self-assembled into fibrils and biocompatible hydrogels. Using high-resolution cryoelectron microscopy (cryo-EM), we are able to determine the atomic structure for two different coexisting forms of the fibril... More
SUMMARYThe self-assembly of designed peptides into filaments and other higher-order structures has been the focus of intense interest because of the potential for creating new biomaterials and biomedical devices. These peptide assemblies have also been used as models for understanding biological processes, such as the pathological formation of amyloid. We investigate the assembly of an octapeptide sequence, Ac-FKFEFKFE-NH 2 , motivated by prior studies that demonstrated that this amphipathic strand peptide self-assembled into fibrils and biocompatible hydrogels. Using high-resolution cryoelectron microscopy (cryo-EM), we are able to determine the atomic structure for two different coexisting forms of the fibrils, containing four and five sandwich protofilaments, respectively. Surprisingly, the inner walls in both forms are parallel sheets, while the outer walls are antiparallel sheets. Our results demonstrate the chaotic nature of peptide self-assembly and illustrate the importance of cryo-EM structural analysis to understand the complex phase behavior of these materials at near-atomic resolution.Graphical AbstractPeptide assemblies are commonly employed as in vivo biomaterials in therapeutic applications; however, limited information is usually available on the structure of the assemblies and its influence on the biological mechanism of action. Cryo-EM is employed here for the structural analysis of assemblies derived from amphipathic sheet oligopeptide KFE8 at near-atomic resolution. The structure of corresponding filaments depends strongly on assembly conditions. This process may be indicative of a more general phenomenon of chaotic behavior in peptide folding and assembly.
