1. Lactoferrin binding protein B – a bi-functional bacterial receptor protein.
- Author
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Ostan, Nicholas K. H., Yu, Rong-Hua, Ng, Dixon, Lai, Christine Chieh-Lin, Pogoutse, Anastassia K., Sarpe, Vladimir, Hepburn, Morgan, Sheff, Joey, Raval, Shaunak, Schriemer, David C., Moraes, Trevor F., and Schryvers, Anthony B.
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LACTOFERRIN , *CARRIER proteins , *LIPOPROTEINS , *IRON proteins , *NEISSERIA meningitidis , *GRAM-negative bacterial diseases , *PEPTIDE antibiotics - Abstract
Lactoferrin 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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