Zinc finger protein 365 is a new maternal LPS-binding protein that defends zebrafish embryos against gram-negative bacterial infections
Zinc finger protein 365 is a new maternal LPS-binding protein that defends zebrafish embryos against gram-negative bacterial infections
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锌指蛋白 365 是一种新的母体 LPS 结合蛋白，可保护斑马鱼胚胎免受革兰氏阴性细菌感染
DOI：
10.1096/fj.201700694r
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发表时间：
2018-02-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Shicui
中科院分区：
文献类型：
--
作者：
Du, Xiaoyuan;Zhou, Yang;Zhang, Shicui
锌指蛋白365(ZNF365)广泛存在于动物体内，但其功能和机制尚不清楚。在这里，我们清楚地证明了斑马鱼ZNF365是一种新发现的内毒素结合蛋白，能够与革兰氏阴性细菌大肠杆菌、鳗弧菌和嗜水气单胞菌相互作用，并作为一种能够直接杀死细菌的抗菌效应分子发挥作用。我们还揭示了由ZnF_C2H2结构域组成的N-末端残基30-55对于ZNF365的抗菌活性是必不可少的。重要的是，向早期胚胎中微量注射重组ZNF365显著提高了胚胎对致病性嗜水气单胞菌攻击的抵抗力，而向胚胎中注入ZNF365吗啉来下调ZNF365的表达，显著降低了胚胎对致病性嗜水气单胞菌攻击的抵抗力。此外，具有体外抗菌活性的N端肽Z(30-55)也能促进胚胎对嗜水气单胞菌的抗性，而无体外抗菌活性的N端肽Z(56-345)则不能促进胚胎对嗜水气单胞菌的抗性。综上所述，这些结果表明ZNF365是一种母体内毒素结合蛋白，可以保护斑马鱼早期胚胎免受病原性攻击，这是ZNF365蛋白的一个新角色。这项工作也为锌指蛋白的免疫功能提供了新的见解，锌指蛋白广泛分布于各种动物中。
Zinc finger protein 365 (ZNF365) is widespread in animals, but its function and mechanism remains poorly defined. Here we clearly demonstrate that zebrafish ZNF365 is a newly identified LPS-binding protein capable of interacting with the gram-negative bacteria Escherichia coli, Vibrio anguillarum, and Aeromonas hydrophila, and functions as an antibacterial effector molecule capable of directly killing the bacteria. We also reveal that N-terminal residues 30-55 consisting of the ZnF_C2H2 domain are indispensable for ZNF365 antimicrobial activity. Importantly, microinjection of recombinant ZNF365 into early embryos significantly enhanced the resistance of the embryos against pathogenic A. hydrophila challenge, whereas down-regulation of ZNF365 by injection of znf365 morpholino into embryos considerably lowered their resistance against A. hydrophila challenge. Furthermore, the N-terminal peptide Z(30-55) with in vitro antibacterial activity also promoted the resistance of embryos against A. hydrophila, but the peptide Z(56-345) without in vitro antibacterial activity did not. Collectively, these results indicate that ZNF365 is a maternal LPS-binding protein that can protect the early embryos of zebrafish against pathogenic attacks, a novel role to be assigned to ZNF365 proteins. This work also provides new insights into the immunologic function of the zinc finger proteins that are widely distributed in various animals.