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Necator americanus Ancylostoma Secreted Protein-2 (Na-ASP-2) Binds an Ascaroside (ascr#3) in Its Fatty Acid Binding Site
Frontiers in Chemistry ( IF 5.5 ) Pub Date : 2020-11-25 , DOI: 10.3389/fchem.2020.608296
Ola El Atab , Rabih Darwiche , Nathanyal J. Truax , Roger Schneiter , Kenneth G. Hull , Daniel Romo , Oluwatoyin A. Asojo

During their infective stages, hookworms release excretory-secretory (E-S) products, small molecules, and proteins to help evade and suppress the host's immune system. Small molecules found in E-S products of mammalian hookworms include nematode derived metabolites like ascarosides, which are composed of the sugar ascarylose linked to a fatty acid side chain. The most abundant proteins found in hookworm E-S products are members of the protein family known as Ancylostoma secreted protein (ASP). In this study, two ascarosides and their fatty acid moieties were synthesized and tested for in vitro binding to Na-ASP-2 using both a ligand competition assay and microscale thermophoresis. The fatty acid moieties of both ascarosides tested and ascr#3, an ascaroside found in rat hookworm E-S products, bind to Na-ASP-2's palmitate binding cavity. These molecules were confirmed to bind to the palmitate but not the sterol binding sites. An ascaroside, oscr#10, which is not found in hookworm E-S products, does not bind to Na-ASP-2. More studies are required to determine the structural basis of ascarosides binding by Na-ASP-2 and to understand the physiological significance of these observations.



中文翻译:

美洲轮虫Anocylostoma分泌蛋白2(Na-ASP-2)在其脂肪酸结合位点结合了A虫苷(ascr#3)。

在感染阶段,钩虫释放出分泌分泌物(ES)产品,小分子和蛋白质,以帮助逃避和抑制宿主的免疫系统。在哺乳动物钩虫的ES产品中发现的小分子包括线虫衍生的代谢产物(例如a虫病),其由连接至脂肪酸侧链的糖Ascarylose组成。钩虫ES产品中发现的最丰富的蛋白质是该蛋白质家族的成员血管瘤分泌蛋白(ASP)。在这项研究中,合成了两个a螨苷及其脂肪酸部分,并测试了体外 绑定到 -ASP-2使用配体竞争测定和微尺度热泳。在大鼠钩虫ES产品中检测到的a虫苷和ascr#3(一种scar虫苷)的脂肪酸部分均与Na-ASP-2棕榈酸酯结合腔。确认这些分子与棕榈酸酯结合,但不与固醇结合位点结合。在钩虫ES产品中找不到的一种scar虫苷oscr#10不会与-ASP-2。需要更多的研究来确定by虫苷结合的结构基础。-ASP-2并了解这些观察结果的生理意义。

更新日期:2020-12-17
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