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.
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 multiplex vaccines and/or novel drugs targeting TEMs in the schistosome tegument.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD 4006, Australia.
authors.forename: Xinying
authors.initials: X
authors.lastname: Jia
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD 4006, Australia; The University of Queensland, School of Veterinary Sciences, Gatton, QLD 4343, Australia.
authors.forename: Leigh
authors.initials: L
authors.lastname: Schulte
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Queensland Tropical Health Alliance, James Cook University, Cairns, QLD 4878, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Queensland Tropical Health Alliance, James Cook University, Cairns, QLD 4878, Australia.
authors.forename: Darren
authors.initials: D
authors.lastname: Pickering
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Queensland Tropical Health Alliance, James Cook University, Cairns, QLD 4878, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Pearson
authors.affiliation: The University of Queensland, Centre for Advanced Imaging, Brisbane, QLD 4072, Australia.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mobli
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.
authors.forename: Alun
authors.initials: A
authors.lastname: Jones
authors.affiliation: The University of Queensland, School of Biomedical Sciences, Brisbane, QLD 4072, Australia.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Rosengren
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Queensland Tropical Health Alliance, James Cook University, Cairns, QLD 4878, Australia.
authors.forename: Norelle L
authors.initials: NL
authors.lastname: Daly
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD 4006, Australia.
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Gobert
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD 4006, Australia; The University of Queensland, School of Veterinary Sciences, Gatton, QLD 4343, Australia.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Jones
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD 4006, Australia; The University of Queensland, School of Biomedical Sciences, Brisbane, QLD 4072, Australia. Electronic address: Jason.Mulvenna@qimrberghofer.edu.au.
authors.forename: Jason
authors.initials: J
authors.lastname: Mulvenna
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology; D000947:Antigens, Helminth; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology; D002462:Cell Membrane / Q000737:chemistry* / Q000276:immunology; D015801:Helminth Proteins; D006801:Humans; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000097:blood* / Q000276:immunology; D059470:Tetraspanins / Q000737:chemistry* / Q000276:immunology
chemical_list: D000941:Antigens; D000942:Antigens, Bacterial; D000947:Antigens, Helminth; D001426:Bacterial Proteins; D015801:Helminth Proteins; C000589037:TSP-2 protein, Schistosoma mansoni; D059470:Tetraspanins
keywords: Membrane Proteins; Protein Structure; Proteomics; Schistosoma mansoni; Schistosomiasis; Tetraspanins; Vaccines