Guest Seminar  - Proteins with Unconventional Chemical Topology

Chemical topology has emerged as a unique dimension for protein engineering. Nature has demonstrated the power of protein topology engineering in a small yet elegant set of proteins with nontrivial topology (such as cyclotides and lasso peptides possessing exceptional bioactivity and stability). However, artificial topological proteins remain scarce. In this talk, I will discuss our recent efforts in this direction from the development of genetically encoded protein chemical tools to the cellular synthesis of topological/mechano-proteins and further to their biological significance and potential applications. Through the “assembly-reaction” synergy, we have prepared various topological proteins including cyclic proteins, star proteins, protein catenanes, lasso proteins, protein heterocatenanes and polycatenanes using either passive or active templates. Their unique topologies have been proven by combined techniques such as controlled digestion experiments, NMR spectrometry, and protein crystallography. Among them, proteins with mechanical bonds (“mechanoproteins”) are of particular interest owing to their potential functional benefits such as structure stabilization, quaternary structure control, synergistic multivalency effect and dynamic mechanical sliding/switching properties. Indeed, protein catenanes containing folded structural domains have been found to exhibit enhanced stability toward proteolytic digestion, heat/chemical denaturation, and freeze-thawing treatments, which are highly desired features for enzymes in industry and protein therapeutics. These results suggest that protein topology engineering has quite broad implications and potential applications.