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合成阴离子通道：在人工系统中实现对囊性纤维化跨膜传导调节因子离子渗透途径的精确模拟。

Synthetic anion channels: achieving precise mimicry of the ion permeation pathway of CFTR in an artificial system.

作者信息

Mao Linlin, Hou Shuaimin, Shi Linlin, Guo Jingjing, Zhu Bo, Sun Yonghui, Chang Junbiao, Xin Pengyang

机构信息

State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, NMPA Key Laboratory for Research and Evaluation of Innovative Drug, School of Chemistry and Chemical Engineering, Henan Normal University 46 Jianshe Road Xinxiang 453007 Henan China

Centre in Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic University Macao 999078 China

出版信息

Chem Sci. 2024 Nov 25;16(1):371-377. doi: 10.1039/d4sc06893a. eCollection 2024 Dec 18.

DOI:10.1039/d4sc06893a
PMID:39620072
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11605520/
Abstract

CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), a naturally occurring anion channel essential for numerous biological processes, possesses a positively charged ion conduction pathway within its transmembrane domain, which serves as the core module for promoting the movement of anions across cell membranes. In this study, we developed novel artificial anion channels by rebuilding the positively charged ion permeation pathway of the CFTR in artificial systems. These synthetic molecules can be efficiently inserted into lipid bilayers to form artificial ion channels, which exhibit a preference for anions during the transmembrane transport process. More importantly, the positively charged amino acid residues located in the ion permeation pathway of these artificial channels can promote the transmembrane transport of anions through electrostatic interactions, which is consistent with the mechanism of anion transmembrane transport achieved by CFTR.

摘要

囊性纤维化跨膜传导调节因子（CFTR）是众多生物过程所必需的天然存在的阴离子通道，在其跨膜结构域内拥有一个带正电荷的离子传导途径，该途径作为促进阴离子跨细胞膜移动的核心模块。在本研究中，我们通过在人工系统中重建CFTR带正电荷的离子渗透途径，开发了新型人工阴离子通道。这些合成分子能够高效插入脂质双层以形成人工离子通道，在跨膜运输过程中表现出对阴离子的偏好。更重要的是，这些人工通道离子渗透途径中的带正电荷氨基酸残基可通过静电相互作用促进阴离子的跨膜运输，这与CFTR实现阴离子跨膜运输的机制一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/43225e6fc007/d4sc06893a-f10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/278bc0b17b13/d4sc06893a-f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/94c19208fd5a/d4sc06893a-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/6619212d879e/d4sc06893a-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/a10862097518/d4sc06893a-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/43225e6fc007/d4sc06893a-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/b3ebf45db344/d4sc06893a-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/16260f07841d/d4sc06893a-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/b319774aa7a5/d4sc06893a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/b93e0338e137/d4sc06893a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/278bc0b17b13/d4sc06893a-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/aecda559b0a2/d4sc06893a-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/94c19208fd5a/d4sc06893a-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/6619212d879e/d4sc06893a-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/a10862097518/d4sc06893a-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/11653515/43225e6fc007/d4sc06893a-f10.jpg

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