Résumé
Schistolysins are aerolysin-like proteins, with 2 genes recently discovered by D. Duval and colleagues in the parasitic flatworm Schistosoma mansoni (unpublished data). This organism is the causative agent of intestinal schistosomiasis, which affected 236 million people worldwide in 2019. In 2020, the WHO called for new therapies to support the action of Praziquantel, the most used treatment, to eliminate the disease by 2030 [1].Aerolysin-like proteins are found in all kingdoms of life, originating from bacteria [2], usually as potent attack or defence agents. Schistolysins display structural similarity to this class of proteins, which make them potential β-pore-forming proteins. Our goal is to characterise the structure-function relationships through integrative structural biology. To date, the study of schistolysin 2 (Schi2) is the most advanced. It is produced as a stable octamer, as we were able to identify it by SDS-PAGE, small angle X-ray scattering (SAXS) and native mass spectrometry. We recently solved the structure of octameric Schi2 at 2.6 Å resolution by X-ray crystallography.Two questions arise: does the observed octamer correspond to a pre-pore state and does Schi2 possess cytotoxic activity? According to DALI server results, Schi2 displays a very similar structure to epsilon toxin (PDB: 1UYJ), an aerolysin-like toxin from Clostridium perfringens [3]. To determine the role and activity of Schi2, molecular dynamics and liposome leakage experiments will help assay the interaction with membranes. Also, purified Schi2 is used for cytotoxicity tests. The combination of structural and functional data should allow us to understand the role of this protein in Schistosoma mansoni, and possibly help develop new therapies against schistosomiasis or other applications.