Sumin Hong

Pohang University of Science and Technology

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Wenhao Wu

Beijing National Laboratory for Molecular Sciences

Yajie Liu

Southern Medical University Shenzhen Hospital

Wenbin Zhang

Peking University

Jing Fang

University of South Carolina

Gengxin Liu

Donghua University

Jongcheol Seo

Pohang University of Science and Technology

Fan Zhang

Peking University

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Peking University

Beijing National Laboratory for Molecular Sciences

Zhejiang University

Tianjin Normal University

China Academy of Information and Communications Technology

Southwest Jiaotong University

Guangdong Pharmaceutical University

Fudan University

Beijing Academy of Artificial Intelligence

Applied Materials (United States)

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

Angewandte Chemie International Edition (2020)

Yajie Liu Wenhao Wu Sumin Hong Jing Fang Fan Zhang

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.

Rotaxane

Protein Engineering

Catenane

Synthetic Biology

10.1002/anie.202006727

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Citations (30)

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

Angewandte Chemie (2020)

Yajie Liu Wenhao Wu Sumin Hong Jing Fang Fan Zhang

Abstract 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.

Rotaxane

Catenane

Protein Engineering

10.1002/ange.202006727

Cite

Citations (2)