Structural Variations within the Transferrin Binding Site on Transferrin-binding Protein B, TbpB

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dc.contributor.authorCalmettes, Charles
dc.contributor.authorYu, Rong-hua
dc.contributor.authorSilva, Leslie P.
dc.contributor.authorCurran, Dave
dc.contributor.authorSchriemer, David C.
dc.contributor.authorSchryvers, Anthony B.
dc.contributor.authorMoraes, Trevor F.
dc.date.accessioned2017-08-17T16:25:23Z
dc.date.available2017-08-17T16:25:23Z
dc.date.issued2011-04-08
dc.description.abstractPathogenic bacteria acquire the essential element iron through specialized uptake pathways that are necessary in the iron-limiting environments of the host. Members of the Gram-negative Neisseriaceae and Pasteurellaceae families have adapted to acquire iron from the host iron binding glycoprotein, transferrin (Tf), through a receptor complex comprised of transferring-binding protein (Tbp) A and B. Because of the critical role they play in the host, these surface-exposed proteins are invariably present in clinical isolates and thus are considered prime vaccine targets. The specific interactions between TbpB and Tf are essential and ultimately might be exploited to create a broad-spectrum vaccine. In this study, we report the structure of TbpBs from two porcine pathogens, Actinobacillus pleuropneumoniae and suis. Paradoxically, despite a common Tf target, these swine related TbpBs show substantial sequence variation in their Tf-binding site. The TbpB structures, supported by docking simulations, surface plasmon resonance and hydrogen/deuterium exchange experiments with wild-type and mutant TbpBs, explain why there are structurally conserved elements within TbpB homologs despite major sequence variation that are required for binding Tf.en_US
dc.description.grantingagencyCanadian Foundation for Innovation (CFI), Alberta Heritage Foundation for Medical Research (AHFMR), and Canadian Institutes of Health Research (CIHR).en_US
dc.description.refereedYesen_US
dc.description.sponsorshipWe thank members of Canadian Light Source (CLS) beamline staff at CMCF-08ID-1 for assistance with data collection and members of the Moraes and Schryvers laboratories for valuable discussion.en_US
dc.identifier.citationCalmettes, C., Yu, R., Silva, L. P., Curran, D., Schriemer, D. C., Schryvers, A. B., & Moraes, T. F. (2011). Structural variations within the transferrin binding site on transferrin-binding protein B, TbpB. Journal of Biological Chemistry, 286(14), 12683-12692. doi:10.1074/jbc.M110.206102en_US
dc.identifier.doi10.1074/jbc.M110.206102
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/33875
dc.identifier.urihttp://hdl.handle.net/1880/52191
dc.language.isoenen_US
dc.publisherJournal of Biological Chemistryen_US
dc.publisher.departmentDepartment of Biologyen_US
dc.publisher.institutionUniversity of Torontoen_US
dc.publisher.urlhttp://www.jbc.org/en_US
dc.subjectBacteriaen_US
dc.subjectCell Surface Proteinen_US
dc.subjectIronen_US
dc.subjectProtein Structureen_US
dc.subjectX-ray Crystallographyen_US
dc.subjectBacterial Lipoproteinen_US
dc.subjectBacterial Transferrin Receptoren_US
dc.subjectIron Acquisitionen_US
dc.subjectVaccine Candidateen_US
dc.subjectMembrane Proteinen_US
dc.titleStructural Variations within the Transferrin Binding Site on Transferrin-binding Protein B, TbpBen_US
dc.typejournal article
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