Necator americanus Ancylostoma Secreted Protein-2 ( Na -ASP-2) Binds an Ascaroside (ascr#3) in Its Fatty Acid Binding Site

• Published in: Frontiers in chemistry Vol. 8; p. 608296
• Main Authors: El Atab, Ola, Darwiche, Rabih, Truax, Nathanyal J, Schneiter, Roger, Hull, Kenneth G, Romo, Daniel, Asojo, Oluwatoyin A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17.12.2020
• Subjects: CAP [cysteine-rich secretory protein (CRISP)/antigen 5/pathogenesis related-1 (PR-1)]; Chemistry; lipid binding; sperm coating protein (SCP); TAPs [testis specific proteins (Tpx)/antigen 5 (Ag5)/pathogenesis related-1 (PR-1)/Sc7]; venom allergen-like (VAL); sperm coating protein (SCP); CAP [cysteine-rich secretory protein (CRISP)/antigen 5/pathogenesis related-1 (PR-1)]; TAPs [testis specific proteins (Tpx)/antigen 5 (Ag5)/pathogenesis related-1 (PR-1)/Sc7]; venom allergen-like (VAL); lipid binding
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2020.608296

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 secreted protein (ASP). In this study, two ascarosides and their fatty acid moieties were synthesized and tested for binding to -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 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 -ASP-2. More studies are required to determine the structural basis of ascarosides binding by -ASP-2 and to understand the physiological significance of these observations.