Solution structure, membrane interactions and protein binding partners of the tetraspanin Sm-TSP-2, a vaccine antigen from the human blood fluke Schistosoma mansoni

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.

Item ID: 31639
Item Type: Article (Research - C1)
ISSN: 1083-351X
Date Deposited: 25 Jun 2014 01:19
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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