Ostan, Nicholas K. H.Yu, Rong-HuaNg, DixonLai, Christine Chieh-LinPogoutse, Anastassia K.Sharpe, VladimirHepburn, MorganSheff, JoeyRaval, ShaunakSchriemer, David C.Moraes, Trevor F.Schryvers, Anthony B.2017-05-312017-05-312017-3-3Ostan 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.10062441553-7374http://hdl.handle.net/1880/51987Lactoferrin 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.enAttribution 4.0 InternationalNeisseria meningitidisOuter membrane proteinsPeptidesCross-linkingRecombinant proteinsBinding analysisCrystal structureLysinejournal articleMOP138273298351-2010RGPIN 401975-1110.1371/journal.ppat.100624410.11575/PRISM/33804