Modification of a synthetic LPS-binding domain of anti-lipopolysaccharide factor from shrimp reveals strong structure-activity relationship in their antimicrobial characteristics
Modification of a synthetic LPS-binding domain of anti-lipopolysaccharide factor from shrimp reveals strong structure-activity relationship in their antimicrobial characteristics
复制标题
虾抗脂多糖因子的合成 LPS 结合结构域的修饰揭示了其抗菌特性中强烈的结构-活性关系
DOI：
10.1016/j.dci.2014.03.003
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发表时间：
2014-08-01
影响因子：
2.9
通讯作者：
Xiang, Jianhai
中科院分区：
文献类型：
--
作者：
Guo, Shuyue;Li, Shihao;Xiang, Jianhai
抗脂多糖因子（ALF）是一种小分子蛋白质，具有广谱抗菌活性和一定的抗病毒活性。推测其脂多糖（LPS）结合结构域对其活性起重要作用。然而，迄今为止，还没有报道揭示LPS结合结构域的结构如何影响其生物学功能。本研究设计并合成了中国对虾ALF的LPS结合域肽段（FcALF-LBDc）及其结构修饰的异构体，以分析其结构与抗菌活性的关系。结果表明，FcALF-LBDc对革兰氏阴性菌大肠杆菌和鳗弧菌以及革兰氏阳性菌藤黄微球菌和溶壁微球菌均表现出明显的抗菌活性，MIC范围分别为32-64、2-4、1-2和32-64 μ M。ALF的二硫环和脂多糖结合结构域（LBD）中的碱性氨基酸在其抗菌活性中起关键作用。此外，FcALF-LBDc在体内可抑制白色斑点综合征病毒（WSSV）的增殖，其赖氨酸残基是其抗病毒特性不可缺少的。这是首次尝试证明LPS结合结构域的序列特征对其抗菌活性的影响。(C)2014爱思唯尔有限公司版权所有。
Anti-lipopolysaccharide factor (ALF) is a small protein with broad-spectrum antimicrobial activities and certain antiviral property. Its putative lipopolysaccharide (LPS) binding domain was deduced to be important for its activities. However, there is still no report revealing how the structure of the LPS-binding domain affects its biological function until now. In the present study, we designed and synthesized a peptide corresponding to the LPS-binding domain of ALF from the Chinese shrimp (designated as FcALF-LBDc) and its structure-modified isoforms in order to analyze the relationship between its structure and antimicrobial activities. Results showed that FcALF-LBDc exhibited apparent antibacterial activities against both Gram-negative bacteria Escherichia coli and Vibrio anguillarum and Gram-positive bacteria Micrococcus luteus and Micrococcus lysodeikticus with MIC ranges of 32-64, 2-4, 1-2, and 32-64 mu M, respectively. The disulfide loop and the basic amino acids in the LPS-binding domain (LBD) of ALF played key roles in its antibacterial activities. In addition, FcALF-LBDc could reduce the propagation of white spot syndrome virus (WSSV) in vivo, and its lysine residue is indispensable for its antiviral property. This is the first attempt to testify the effects of the sequence features of the LPS-binding domain on its antimicrobial activities. (C) 2014 Elsevier Ltd. All rights reserved.