Topology: a unique dimension in protein engineering

Controlling protein topology has been a long standing challenge to go beyond their linear configuration defined by the translation mechanism of cellular machinery. In this mini-review, we focus on the topological diversity in proteins and review the major categories of protein topologies known to date, including branched/star proteins, circular proteins, lasso proteins, knotted proteins, and protein catenanes. The discovery of these topologically complex natural proteins and their synthetic pathways, the rational design and recombinant synthesis of artificial topological proteins and their biophysical studies, are summarized and discussed with regard to their general features and broad implications. The complexity of protein topology is recognized and the routes to diverse protein topologies are illustrated. We believe that topology engineering is an important way to modify protein properties without alternating their native sequences and shall bring in valuable dynamic features central to the creation of artificial protein machinery.