%0 Journal Article
%T Lactoferrin binding protein B ¨C a bi-functional bacterial receptor protein
%A Anastassia K. Pogoutse
%A Anthony B. Schryvers
%A Christine Chieh-Lin Lai
%A David C. Schriemer
%A Dixon Ng
%A Joey Sheff
%A Morgan Hepburn
%A Nicholas K. H. Ostan
%A Rong-Hua Yu
%A Shaunak Raval
%A Trevor F. Moraes
%A Vladimir Sarpe
%J -
%D 2017
%R 10.1371/journal.ppat.1006244
%X 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
%K Neisseria meningitidis
%K Outer membrane proteins
%K Cross-linking
%K Recombinant proteins
%K Binding analysis
%K Crystal structure
%K Lysine
%K Glycoproteins
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006244