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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 international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202006727
Subject(s) - modular design , rotaxane , intramolecular force , lasso (programming language) , dimer , computational biology , ring (chemistry) , chemistry , biophysics , topology (electrical circuits) , crystallography , biology , computer science , stereochemistry , mathematics , supramolecular chemistry , world wide web , operating system , organic chemistry , crystal structure , combinatorics
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.