Synthetic K+ Channels Constructed by Rebuilding the Core Modules of Natural K+ Channels in an Artificial System

• Published in: Angewandte Chemie International Edition Vol. 62; no. 8; pp. e202217859 - n/a
• Main Authors: Xin, Pengyang, Xu, Linqi, Dong, Wenpei, Mao, Linlin, Guo, Jingjing, Bi, Jingjing, Zhang, Shouwei, Pei, Yan, Chen, Chang‐Po
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 13.02.2023
• Edition: International ed. in English
• Subjects: Apoptosis; Biological Transport; Cations; Cell membranes; Channels; Cyclodextrins; Homeostasis; Ion Channels; Modules; Permeability; Potassium; Potassium - metabolism; Rebuilding; Rubidium; Selectivity; Sodium; Supramolecular Chemistry; Transmembrane Transport; Transport processes; Transmembrane Transport; Cyclodextrins; Ion Channels; Potassium; Supramolecular Chemistry
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202217859

Different types of natural K+ channels share similar core modules and cation permeability characteristics. In this study, we have developed novel artificial K+ channels by rebuilding the core modules of natural K+ channels in artificial systems. All the channels displayed high selectivity for K+ over Na+ and exhibited a selectivity sequence of K+≈Rb+ during the transport process, which is highly consistent with the cation permeability characteristics of natural K+ channels. More importantly, these artificial channels could be efficiently inserted into cell membranes and mediate the transmembrane transport of K+, disrupting the cellular K+ homeostasis and eventually triggering the apoptosis of cells. These findings demonstrate that, by rebuilding the core modules of natural K+ channels in artificial systems, the structures, transport behaviors, and physiological functions of natural K+ channels can be mimicked in synthetic channels. Rebuilding the core modules of natural K+ channels in an artificial system has led to a biomimetic K+ channel. This channel possesses similar structural features as the natural version, which enables it to replicate the transport behavior and biological function of natural K+ channels.