Lasso Proteins: Modular Design, Cellular Synthesis, and Topological Transformation.

Liu, Yajie; Wu, Wen‐Hao; Hong, Sumin; Fang, Jing; Zhang, Fan; Liu, Geng‐Xin; Seo, Jongcheol; Zhang, Wen‐Bin

Entangled proteins have attracted significant research interest. Herein, we report the first rationally designed lasso proteins, or protein [1]rotaxanes, by using a p53dim‐entwined dimer for intramolecular entanglement and a SpyTag‐SpyCatcher reaction for side‐chain ring closure. The lasso structures were confirmed by proteolytic digestion, mutation, NMR spectrometry, and controlled ligation. Their dynamic properties were probed by experiments such as end‐capping, proteolytic digestion, and heating/cooling. As a versatile topological intermediate, a lasso protein could be converted to a rotaxane, a heterocatenane, and a "slide‐ring" network. Being entirely genetically encoded, this robust and modular lasso‐protein motif is a valuable addition to the topological protein repertoire and a promising candidate for protein‐based biomaterials.

PROTEIN engineering; MODULAR design; BIOMATERIALS; PROTEINS; COOLING

Angewandte Chemie, 2020, Vol 132, Issue 43, p19315

0044-8249

Academic Journal

10.1002/ange.202006727