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: 1-26. doi:10.1074/jbc.M113.531558

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Author 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.
Mulvenna, Jason
Title Solution structure, membrane interactions and protein binding partners of the tetraspanin Sm-TSP-2, a vaccine antigen from the human blood fluke Schistosoma mansoni
Formatted title
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 name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2014-01-15
Sub-type Article (original research)
DOI 10.1074/jbc.M113.531558
Open Access Status DOI
Volume 289
Issue 10
Start page 1
End page 26
Total pages 26
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2015
Language eng
Formatted 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

Capsule
Background: Schistosome tetraspanin Sm-TSP-2 is vaccine antigen.
Results: We describe the structure of large extra-cellular domain of Sm-TSP-2, develop a model of its interactions with Tetraspanin-enriched-microdomain (TEM) proteins and plasma membrane and identify TEM constituents.
Conclusion: Structural conservation of the domain means this model is likely applicable to TSPs in general.
Significance: Tetraspanin-enriched-microdomain proteins provide further targets for multiplex vaccines and/or novel drug targets.
Keyword Membrane proteins
Protein structure
Proteomics
Tetraspanins
Vaccines
Schistosoma mansoni
Schistosomiasis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First Published on January 15, 2014

 
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 13 Feb 2014, 00:45:02 EST by Susan Allen on behalf of Institute for Molecular Bioscience