Self-assembly of Helical Peptide Filaments and Tubes

The rich functional properties of biologically derived helical assemblies provide inspiration for the de novo design of synthetic analogues, which, unconstrained by evolution, can be designed to perform unique functions under conditions that differ from those that commonly occur in the native biological environment. Biologically derived helical protein assemblies encompass a diversity of functional roles that would be desirable to emulate in synthetic systems, including controlled release and delivery, cargo transport, locomotion, energy transduction, and signal transduction and actuation. However, it remains difficult, if not impossible, to achieve this level of structural and functional control, thus far, for synthetic assemblies.

Structural studies of synthetic peptides and proteins provide the best opportunity to create analogues of biologically derived protein filaments to understand the sequence-structure relationship that underlies the the self-assembly process and, ultimately, functional properties. However, the structures of most designed peptide assemblies are not known at high resolution and reliable structural models are not available. Here, we report the cryo-EM analysis of designed peptide assemblies that enables the reconstruction of reliable atomic models. These structural analyses suggest that polymorphism is a common occurrence among designed peptide assemblies. In addition, chaotic behavior is commonly observed in which the observed structure depends strongly on initial conditions. In addition, sequence-structure correlations derived from the analysis of soluble, globular proteins provide limited predictive insight into the reliable design of filamentous peptide nanomaterials. Therefore, high-resolution structural analyses of native and synthetic assemblies are essential to build databases that can be employed as a resource of information to guide reliable structural prediction and sequence design of self-assembling peptides.