Heligmosomoides polygyrus Venom Allergen-like Protein-4 (HpVAL-4) is a sterol binding protein

Asojo, Oluwatoyin A.; Darwiche, Rabih; Gebremedhin, Selam; Smant, G.; Lozano‐Torres, Jose L.; Drurey, Claire; Pollet, Jeroen; Maizels, Rick M.; Schneiter, Roger; Wilbers, Ruud H. P.

doi:10.1016/j.ijpara.2018.01.002

Cited by 20 publications

(29 citation statements)

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“…Na-ASP-2 displayed saturable binding of cholesterol with an apparent dissociation constant Kd of 2.1 µM ( Figure 3A). Na-ASP-2 has similar cholesterol binding affinity as reported for other SCP/TAPS family members from yeast, Saccharomyces cerevisiae (Pry1, 1.9 µM), Brugia malayi (Bm-VAL-1, 0.9 µM), Heligmosomoides polygyrus (Hp-VAL-4, 1.53 µM) and Schistosoma mansoni (Sm-VAL-4, 2.4 µM) (Asojo et al, 2018;Darwiche et al, 2016;Darwiche et al, 2018;Kelleher et al, 2014). Furthermore, addition of equimolar or excess concentration of unlabeled cholesterol reduced binding of the radioligand, indicating that binding is specific as shown in Figure 3A,B.…”

Section: Na-asp-2 Binds Cholesterol and Palmitic Acid In Vitrosupporting

confidence: 59%

“…Our previous studies revealed that palmitic acid specifically binds to this cavity in other SCP/TAPS proteins including pathogen-related in yeast protein 1(Pry1) from Saccharomyces cerevisiae hence the cavity is referred to as the fatty acid-binding cavity (Asojo et al, 2018;Darwiche et al, 2016;Darwiche et al, 2018;Kelleher et al, 2014). While lipid binding had been confirmed for other parasite SCP/TAPS proteins, we solved the structure of Na-ASP-2 prior to the discovery of the lipid binding activity of members of this protein superfamily (Asojo et al, 2005a).…”

Section: Introductionmentioning

confidence: 96%

“…These Ancylostoma secreted protein sometimes referred to as VALs (venom allergen like) are the major protein components of the L3 excretory-secretory (E-S) products that facilitate the evasion and suppression of the host's immune system and have been found in all parasitic nematodes studied to date (Asojo et al, 2018;Darwiche et al, 2018;Gao et al, 2001;Hawdon et al, 1995;Hawdon et al, 1999;Zhan et al, 2003). ASPs belong to the SCP/TAPS (sperm-coating protein / Tpx / antigen 5 / pathogenesis related-1 / Sc7) page 4 superfamily of proteins, NCBI domain cd00168 or Pfam PF00188 (Gibbs et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…and Mg 2+ (Asojo et al, 2018;Asojo et al, 2011;Darwiche et al, 2018;Gibbs et al, 2008;Mason et al, 2014;Wang et al, 2010). Distinct lipid binding sites have been verified in SCP/TAPS proteins, including phosphatidylinositol binding regions on the surface of human golgi-associated plant pathogenesis-related protein 1 (GAPR-1) (Darwiche et al, 2016;van Galen et al, 2012;Van Galen et al, 2010;Xu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Distinct lipid binding sites have been verified in SCP/TAPS proteins, including phosphatidylinositol binding regions on the surface of human golgi-associated plant pathogenesis-related protein 1 (GAPR-1) (Darwiche et al, 2016;van Galen et al, 2012;Van Galen et al, 2010;Xu et al, 2012). A sterol binding caveolin-binding motif (CBM) of the yeast page 5 CAP proteins required for in vivo transport of cholesterol has also been identified in diverse SCP/TAPS proteins (Asojo et al, 2018;Choudhary et al, 2014;Darwiche et al, 2017a;Darwiche et al, 2016;Darwiche et al, 2018;Darwiche et al, 2017b;Kelleher et al, 2014). Furthermore, a hydrophobic channel that binds leukotrienes with sub-micromolar affinities, allows tablysin-15, an SCP/TAPS protein from the horsefly Tabanus yao, to function as an anti-inflammatory scavenger of eicosanoids (Xu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Necator americanus Ancylostoma secreted protein-2 (Na-ASP-2) selectively binds an ascaroside (ascr#3)

Atab

Darwiche

Truax

et al. 2020

Preprint

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During their infective stages, hookworms release excretory-secretory (E-S) products, including 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. Ascarosides play vital roles in signaling, development, reproduction, and survival. The most abundant proteins found in hookworm E-S products are members of the protein family known as Ancylostoma secreted protein (ASP). ASP belongs to the SCP/TAPS (sperm-coating protein / Tpx / antigen 5 / pathogenesis related-1 / Sc7) superfamily of proteins, members of which have previously been shown to bind to eicosanoids and fatty acids. These molecules are structurally similar to the fatty acid moieties of ascarosides. The objective of this study was to determine if the hookworm ASP; N. americanus Ancylostoma secreted protein 2 (Na-ASP-2) binds to the ascarosides or their fatty acid moieties. We describe investigations of our hypothesis that there is a functional relationship between the major secreted proteins and signaling small molecules found in hookworm E-S products. To accomplish this, several ascarosides and their fatty acid moieties were synthesized and tested for in vitro binding to Na-ASP-2 using a ligand competition assay and microscale thermophoresis. Our results reveal that the fatty acid moieties of the ascarosides, bind specifically to the palmitic acid binding cavity of Na-ASP-2. Additionally, ascr#3, an ascaroside that is present in mammalian hookworm E-S products binds to the palmitic acid binding cavity of Na-ASP-2, whereas oscr#10 which is not found in hookworm E-S products does not bind. Future studies are required to determine the structural basis of ascaroside binding by Na-ASP-2 and to understand the physiological significance of these observations.

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Section: Na-asp-2 Binds Cholesterol and Palmitic Acid In Vitrosupporting

confidence: 59%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Necator americanus Ancylostoma secreted protein-2 (Na-ASP-2) selectively binds an ascaroside (ascr#3)

Atab

Darwiche

Truax

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2017–2018

Harvey

2021

Mass Spectrometry Reviews

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This review is the tenth update of the original article published in 1999 on the application of matrix‐assisted laser desorption/ionization mass spectrometry (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2018. Also included are papers that describe methods appropriate to glycan and glycoprotein analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, new methods, matrices, derivatization, MALDI imaging, fragmentation and the use of arrays. The second part of the review is devoted to applications to various structural types such as oligo‐ and poly‐saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Most of the applications are presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. The reported work shows increasing use of combined new techniques such as ion mobility and highlights the impact that MALDI imaging is having across a range of diciplines. MALDI is still an ideal technique for carbohydrate analysis and advancements in the technique and the range of applications continue steady progress.

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Molecular variability of the Ancylostoma secreted Protein-2 (Aca-asp-2) gene from Ancylostoma caninum contributes to expand information on population genetic studies of hookworms

Furtado

Miranda

Tennessen

et al. 2023

Experimental Parasitology

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Heligmosomoides polygyrus Venom Allergen-like Protein-4 (HpVAL-4) is a sterol binding protein

Abstract: Graphical abstract

Cited by 20 publications

References 71 publications

Necator americanus Ancylostoma secreted protein-2 (Na-ASP-2) selectively binds an ascaroside (ascr#3)

Necator americanus Ancylostoma secreted protein-2 (Na-ASP-2) selectively binds an ascaroside (ascr#3)

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2017–2018

Molecular variability of the Ancylostoma secreted Protein-2 (Aca-asp-2) gene from Ancylostoma caninum contributes to expand information on population genetic studies of hookworms

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