Jia, Xinying, Schulte, Leigh, Loukas, Alex, Pickering, Darren, Pearson, Mark, Mobli, Mehdi, Jones, Alun, Rosengren, Karl J., Daly, Norelle L., Gobert, Geoffrey N., Jones, Malcolm K., Craik, David J., and Mulvenna, Jason (2014) Solution structure, membrane interactions and protein binding partners of the tetraspanin Sm-TSP-2, a vaccine antigen from the human blood fluke Schistosoma mansoni. Journal of Biological Chemistry, 289 (10). pp. 7151-7163.

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Abstract

The tetraspanins (TSPs) are a family of integral membrane proteins that are ubiquitously expressed at the surface of eukaryotic cells. TSPs mediate a range of processes at the surface of the plasma membrane by providing a scaffold for the assembly of protein complexes known as tetraspanin-enriched microdomains (TEMs). We report here the structure of the surface exposed EC2 domain from Sm-TSP-2, a TSP from Schistosoma mansoni and one of the better prospects for the development of a vaccine against schistosomiasis. This is the first solution structure of this domain and our investigations of its interactions with lipid micelles provide a general model for interactions between TSPs, membranes and other proteins. Using chemical cross-linking, eight potential protein constituents of Sm-TSP-2 mediated TEMs were also identified. These include proteins important for membrane maintenance and repair, providing further evidence for the functional role of Sm-TSP-2 and Sm-TSP-2-mediated TEMs. The identification of calpain, Sm29 and fructose-bisphosphate aldolase, themselves potential vaccine antigens, suggests that the Sm-TSP-2 mediated TEMs could be disrupted via multiple targets. The identification of further Sm-TSP-2-mediated TEM proteins increases the available candidates for multi-plex vaccines and/or novel drugs targeting TEMs in the schistosome tegument.

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