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

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. © 2017 ostan et al.