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Lasso Proteins: Modular Design, Cellular Synthesis, and Topological Transformation
Author(s) -
Liu Yajie,
Wu WenHao,
Hong Sumin,
Fang Jing,
Zhang Fan,
Liu GengXin,
Seo Jongcheol,
Zhang WenBin
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202006727
Subject(s) - rotaxane , intramolecular force , modular design , chemistry , catenane , dimer , protein engineering , computational biology , biophysics , biochemistry , stereochemistry , crystallography , biology , computer science , supramolecular chemistry , crystal structure , enzyme , organic chemistry , molecule , operating system
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.