Designability of α-Helical Protein Filaments

Helix-helix interactions are mediated through highly designable interfaces within tertiary and quaternary structures of proteins and protein assemblies. The structural regularity of these interfaces suggests that ordered self-assembled structures could be constructed from implementation of these interactions between appropriately designed helical protomers. This review summarizes the current understanding of helix-helix interactions within different classes of naturally occurring α-helical protein filaments. The implications of this structural information for the de novo design of synthetic filamentous nanomaterials will be discussed with reference to examples in which these principles have been successfully implemented. A specific case study will focus on the designability of cross-α helical filaments, a recently discovered structural class in which the helical protomers are arranged in a perpendicular orientation with respect to the protofilament axis. This discussion will include an evaluation of the frequency of occurrence of cross-α interfaces in the PDB, the effectiveness of structural prediction from sequence information, and the potential for de novo design of interfaces that promote cross-α interactions.