Stepanka Nedvedova (Prague / CZ), Dr. Florence Guilliere (Villeurbanne / FR), Olivier Walker (Villeurbanne / FR), Mrs. Kristýna Peterková (Prague / CZ), Dr. Jan Dvořák (Prague / CZ), Adriana Erica Miele (Villeurbanne / FR), Maggy Hologne (Villeurbanne / FR)
Abstract text
Schistosomiasis is a parasitic disease caused by trematodes affecting the lives of millions of people worldwide1. Our work focuses on Schistosoma mansoni, the most widespread species of schistosomes infecting humans. Adult parasites reside in the circulatory system and lay eggs that need transiting from the endothelium of the blood vessel via host tissues into the gut lumen to be excreted to perpetuate the life cycle2. However, many of them remain trapped in host tissues, where they induce inflammation and chronic debilitating pathology. Eggs produce many bioactive molecules2,3, whose specific role is still yet to be characterized.
We decided to focus on a significantly upregulated group of proteins named MEG proteins (micro-exon gene). These proteins are unique not only because of their genetic structure but also because they are specific to Schistosomatidae3. Due to alternative splicing, almost all members of the more than 30 families of MEGs generate several isoforms4. They do not show relevant homologies to other proteins in the UniProt database5, and their structure is still unresolved, as well as their specific role in egg-host interaction.
We selected members of the MEG-2 and MEG-3 families. Our approach using standard protein engineering tools to produce recombinant proteins failed to obtain enough material. Therefore, we decided to divide the sequences into short synthetic overlapping peptides. In particular, we subdivided 3 isoforms of the MEG-2.1 family into 8 peptides. We collected a series of 2D NMR homonuclear and heteronuclear spectra, measured in the natural abundance of 13C and 15N. The attribution of the peaks in the 2D spectra, in combination with distance geometry and energy minimization software, allowed us to determine the structures of these peptides belonging to 2 out of the 3 isoforms. Here we present the first structural information on S. mansoni MEG proteins, which can serve to infer the structure of other MEG family members. Resolving the structure is the first step toward the elucidation of MEGs role in host-parasite interactions.
1. WHO. Schistosomiasis. 2022 https://www.who.int/news-room/fact-sheets/detail/schistosomiasis
2. Costain AH et al. Front immunol 2018, 9: 3042.
3. Li XH et al. PLoS NTD 2018; 12.2: e0006235.
4. DeMarco R, et al. Genome Res. 2010; 20(8):1112-21.
5. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res. 2021; 49.D1: D480-D489.