Lactoferrin binding protein B - a bi-functional bacterial receptor protein

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dc.contributor.authorOstan, Nicholas K. H.
dc.contributor.authorYu, Rong-Hua
dc.contributor.authorNg, Dixon
dc.contributor.authorLai, Christine Chieh-Lin
dc.contributor.authorPogoutse, Anastassia K.
dc.contributor.authorSharpe, Vladimir
dc.contributor.authorHepburn, Morgan
dc.contributor.authorSheff, Joey
dc.contributor.authorRaval, Shaunak
dc.contributor.authorSchriemer, David C.
dc.contributor.authorMoraes, Trevor F.
dc.contributor.authorSchryvers, Anthony B.
dc.date.accessioned2017-05-31T16:16:27Z
dc.date.available2017-05-31T16:16:27Z
dc.date.issued2017-3-3
dc.description.abstractLactoferrin binding protein B (LbpB) is a bi-lobed outer membrane-bound lipoprotein that comprises part of the lactoferrin (Lf) receptor complex in Neisseria meningitidis and other Gram-negative pathogens. Recent studies have demonstrated that LbpB plays a role in protecting the bacteria from cationic antimicrobial peptides due to large regions rich in anionic residues in the C-terminal lobe. Relative to its homolog, transferrin-binding protein B (TbpB), there currently is little evidence for its role in iron acquisition and relatively little structural and biophysical information on its interaction with Lf. In this study, a combination of crosslinking and deuterium exchange coupled to mass spectrometry, information-driven computational docking, bio-layer interferometry, and site-directed mutagenesis was used to probe LbpB:hLf complexes. The formation of a 1:1 complex of iron-loaded Lf and LbpB involves an interaction between the Lf C-lobe and LbpB N-lobe, comparable to TbpB, consistent with a potential role in iron acquisition. The Lf N-lobe is also capable of binding to negatively charged regions of the LbpB C-lobe and possibly other sites such that a variety of higher order complexes are formed. Our results are consistent with LbpB serving dual roles focused primarily on iron acquisition when exposed to limited levels of iron-loaded Lf on the mucosal surface and effectively binding apo Lf when exposed to high levels at sites of inflammation.en_US
dc.description.refereedYes
dc.description.sponsorshipThis work was supported by Grant MOP138273 from the Canadian Institutes of Health Research (CIHR - http://www.cihr-irsc.gc.ca/e/193.html) for ABS; a Natural Sciences and Engineering Research Council of Canada (NSERC -https://www.canada.ca/en/science-engineering-research.html) Discovery Grant 298351-2010 and the Canada Foundation for Innovation (CFI - https://www.innovation.ca/) for DCS; a NSERC grant (RGPIN 401975-11) as well as with instrumentation and infrastructure support provided by Canadian Foundation for Innovation (CFI), and Ontario Ministry of Education and Innovation for TFM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.identifier.citationOstan NKH, Yu R-H, Ng D, Lai CC-L, Pogoutse AK, Sarpe V, et al. (2017) Lactoferrin binding protein B - a bi-functional bacterial receptor protein. PLoS Pathog 13(3): e1006244. https://doi.org/10.1371/journal.ppat.1006244en_US
dc.identifier.doi10.1371/journal.ppat.1006244
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/33804
dc.identifier.grantnumberMOP138273
dc.identifier.grantnumber298351-2010
dc.identifier.grantnumberRGPIN 401975-11
dc.identifier.issn1553-7374en_US
dc.identifier.urihttp://hdl.handle.net/1880/51987
dc.language.isoenen_US
dc.publisherPLOS Pathogens
dc.publisher.departmentMicrobiology & Infectious Diseases
dc.publisher.facultyCumming School of Medicine
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.urlhttp://journals.plos.org/plospathogensen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectNeisseria meningitidis
dc.subjectOuter membrane proteins
dc.subjectPeptides
dc.subjectCross-linking
dc.subjectRecombinant proteins
dc.subjectBinding analysis
dc.subjectCrystal structure
dc.subjectLysine
dc.titleLactoferrin binding protein B - a bi-functional bacterial receptor protein
dc.typejournal article
thesis.degree.disciplineBiochemistry
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