The Role of LbpB in Iron Acquisition and Cellular Defense in Neisseria meningitidis
Abstract
Lactoferrin binding protein B (LbpB) is a bi-lobed outer membrane-bound lipoprotein that comprises part of the lactoferrin (Lf) receptor complex in many Gram-negative pathogens. Recent studies have demonstrated that the LbpB protein expressed by Neisseria meningitidis - a causative agent and major contributor to bacterial meningitis - 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 homologue, transferrin-binding protein (TbpB), there is little evidence for its role in iron acquisition and relatively little structural and biophysical information on its interaction with Lf. Nevertheless, there have been several published structural models on the LbpB-Lf interaction that are incompatible. In this study I will present comparative experimental data regarding the LbpB-Lf interaction and TbpB-Tf interaction.
Using biophysical data to determine tertiary structure information, I have constructed a new model of LbpB that forms the basis for a new LbpB:Lf interaction. Our data suggests a 1:1 complex of LbpB:hLf is consistent with an LbpB-N/hLf-C binding mode, consistent with a role in iron acquisition. A 2:1 complex of LbpB:hLf:LbpB contains both an LbpB-N/hLf-C interaction as well as an LbpB-C/hLf-N interaction directly with the anti-microbial peptide lactoferricin. We thus show a novel way in which the LbpB from N. meningitidis may sequester anti-microbial peptides, or hinder proteolytic derivation of lactoferricin from lactoferrin by forming large cross-linked complexes of lactoferrin.
Description
Keywords
Biology--Cell, Immunology, Biochemistry
Citation
Ostan, N. (2016). The Role of LbpB in Iron Acquisition and Cellular Defense in Neisseria meningitidis (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28331