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蛋白质折叠诱导的二维阳离子簇在细胞内膜固有通透性中的重要性。

Importance of two-dimensional cation clusters induced by protein folding in intrinsic intracellular membrane permeability.

作者信息

Negi Shigeru, Hamori Mami, Kawahara-Nakagawa Yuka, Imanishi Miki, Kurehara Miku, Kitada Chieri, Kawahito Yuri, Kishi Kanae, Manabe Takayuki, Kawamura Nobuyuki, Kitagishi Hiroaki, Mashimo Masato, Shibata Nobuhito, Sugiura Yukio

机构信息

Faculty of Pharmaceutical Science, Doshisha Women's University, Koudo Kyotanabe Kyoto 610-0395 Japan

Graduate School of Life Science, University of Hyogo 3-2-1 Kouto, Kamigori-cho Ako-gun Hyogo 678-1297 Japan.

出版信息

RSC Chem Biol. 2022 Jul 13;3(8):1076-1084. doi: 10.1039/d2cb00098a. eCollection 2022 Aug 3.

DOI:10.1039/d2cb00098a
PMID:35975000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9347356/
Abstract

We investigated the cell penetration of Sp1 zinc finger proteins (Sp1 ZF) and the mechanism which the total cationic charge and distribution of cationic residues on the protein surface affect intracellular trafficking. Sp1 ZFs showed intrinsic cell membrane permeability. The intracellular transfer of Sp1 ZFs other than 1F3 was dependent on the total cationic charge. Investigation of the effect of cationic residue distribution on intracellular membrane permeability revealed that the cellular uptake of unfolded Zn-non-coordinating Ala mutants was lower than that of the wild type. Therefore, the total cationic charge and distribution of cationic residues on the protein played crucial roles in intracellular translocation. Mutational studies revealed that the two-dimensional cation cluster on the protein surface significantly improved their cellular uptake. This study will contribute to the design of artificial cargoes that can efficiently transport target substances into cells.

摘要

我们研究了Sp1锌指蛋白（Sp1 ZF）的细胞穿透情况，以及蛋白质表面总阳离子电荷和阳离子残基分布影响细胞内运输的机制。Sp1 ZF显示出固有的细胞膜通透性。除1F3外，Sp1 ZF的细胞内转运取决于总阳离子电荷。对阳离子残基分布对细胞内膜通透性影响的研究表明，未折叠的锌非配位丙氨酸突变体的细胞摄取低于野生型。因此，蛋白质表面的总阳离子电荷和阳离子残基分布在细胞内转运中起关键作用。突变研究表明，蛋白质表面的二维阳离子簇显著提高了它们的细胞摄取。这项研究将有助于设计能够有效地将目标物质转运到细胞内的人工载体。

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本文引用的文献

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