Biochemical characterization and comparison of aspartylglucosaminidases secreted in venom of the parasitoid wasps Asobara tabida and Leptopilina heterotoma

Abstract

Aspartylglucosaminidase (AGA) is a low-abundance intracellular enzyme that plays a key role in the last stage of glycoproteins degradation, and whose deficiency leads to human aspartylglucosaminuria, a lysosomal storage disease. Surprisingly, high amounts of AGA-like proteins are secreted in the venom of two phylogenetically distant hymenopteran parasitoid wasp species, Asobara tabida (Braconidae) and Leptopilina heterotoma (Cynipidae). These venom AGAs have a similar domain organization as mammalian AGAs. They share with them key residues for autocatalysis and activity, and the mature α- and β-subunits also form an (αβ)2 structure in solution. Interestingly, only one of these AGAs subunits (α for AtAGA and β for LhAGA) is glycosylated instead of the two subunits for lysosomal human AGA (hAGA), and these glycosylations are partially resistant to PGNase F treatment. The two venom AGAs are secreted as fully activated enzymes, they have a similar aspartylglucosaminidase activity and are both also efficient asparaginases. Once AGAs are injected into the larvae of the Drosophila melanogaster host, the asparaginase activity may play a role in modulating their physiology. Altogether, our data provide new elements for a better understanding of the secretion and the role of venom AGAs as virulence factors in the parasitoid wasps’ success.

Variation in the Venom of Parasitic Wasps, Drift, or Selection? Insights From a Multivariate QST Analysis

“…RhoGAP (LhGAP2) 10B28 1 Aspartylglucosaminidase 23 An aspartylglucosaminidase (AGA), a usually lysosomal enzyme involved in the catabolism of N-linked oligosaccharides of glycoproteins, was found to be abundant in L. heterotoma venom as well as in the venom of Asobara tabida (Moreau et al, 2004;Vinchon et al, 2010;Colinet et al, 2013a;Coulette et al, 2017).…”

Immune Cell Production Is Targeted by Parasitoid Wasp Virulence in a Drosophila–Parasitoid Wasp Interaction

“…Further, while A. tabida is the most closely related of the well-studied parasitoid species to Asobara sp. AsDen , its venom has been shown to cause paralysis and inhibit host development with only limited immune-suppressive effects [ 36 , 75 , 76 , 77 , 78 , 79 ]. This is not entirely unexpected, as other closely related parasitoid species have distinct virulence strategies and venom composition [ 37 , 38 , 80 ].…”

Parasitoid wasp venom targets host immune cell production in aDrosophila-parasitoid interaction

“…Further, while A. tabida is the most closely related of the wellstudied parasitoid species to Asobara sp. AsDen, its venom has been shown to cause paralysis and inhibit host development with only limited immune-suppressive effects [36,[75][76][77][78][79]. This is not entirely unexpected, as other closely related parasitoid species have distinct virulence strategies and venom composition [37,38,80].…”