Systematic discovery and feature analysis of intertwined symmetric protein motifs for topology engineering

Abstract

Naturally occurring nontrivial protein topologies not only draw increasing attention on the relationships between topology and protein function, but also stimulate research endeavors in harnessing topology as a unique dimension for protein engineering. However, artificial design and synthesis of protein topologies is still in its infancy with successes only on a few simple topologies and its development is limited by the small number of intertwined protein motifs known to date. Herein, we report a systematic framework for the discovery of symmetric intertwined protein motifs from Protein Data Bank. The symmetric protein assemblies were screened based on their calculated Gauss linking number to assess their extent of chain intertwining. Then, the potential of such symmetric intertwined motifs in designing complex protein topologies is evaluated based on several parameters, including buried surface area, N-C terminal distances and so on, giving rise to a library of premium intertwined motifs useful for protein topology engineering. Taking C2 assemblies for example, the potential biological significances of chain intertwining in protein architectures are also discussed based on the analysis of their postulated biological functions. With an expanded toolbox of intertwined motifs, the design space of topological proteins would be greatly expanded to enable a broader scope for the application of protein topology engineering.