Cellular Synthesis of Topological Proteinsa
Wen-Bin Zhang is currently an Assistant Professor at the College of Chemistry and Molecular Engineering of Peking University. He received his BS from Peking University in 2004 and his PhD in Polymer Science from the University of Akron in 2010. He continued there as a postdoc for one year, before moving to Caltech for a second postdoc. His research in the past decade has been the pursuit of precision in macromolecular science at both molecular and supramolecular level. His goal is to integrate the design principles and building blocks of both synthetic and biological polymers for the development of precision macromolecules with unique functions for health-related applications. He received the “1000 Talent Award (Youth)” in 2013 and the “Distinguished Lectureship Award” from the Chemical Society of Japan in 2017. He also serves as the editorial board of rising stars for the journal Chinese Journal of Chemistry (since 2017), the executive board member for the journal Polymer (since 2019), and the committee member for the Division of Supramolecular Chemistry, Chinese Chemical Society (since 2018).
Cellular Synthesis of Topological Proteins
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China
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 the field of protein topology engineering from the development of genetically encoded protein chemical tools to the cellular synthesis of topological/mechano-proteins and further to the their biological significance and potential applications. Through strategies such as the “assembly-reaction” synergy and the active-template method, we have prepared various topological proteins including cyclic proteins, star proteins, protein catenanes, lasso proteins, protein heterocatenanes and polycatenanes. 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. Specifically, 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 topology is indeed a unique dimension for protein engineering.
Wang, X.-W.; Zhang, W.-B. Chemical Topology and Complexity of Protein Architectures. Trends Biochem. Sci. 2018, 43, 806-817.