Lactoferrin binding protein B - a bi-functional bacterial receptor protein
| Autor: | Trevor F. Moraes, Christine Chieh-Lin Lai, Shaunak Raval, Nicholas Ostan, Anastassia K. Pogoutse, David C. Schriemer, Joey G. Sheff, Rong-hua Yu, Vladimir Sarpe, Anthony B. Schryvers, Morgan Hepburn, Dixon Ng |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular 0301 basic medicine Receptor complex Cell Membranes Plasma protein binding Neisseria meningitidis Pathology and Laboratory Medicine Biochemistry Physical Chemistry Mass Spectrometry Binding Analysis Protein A/G Medicine and Health Sciences Cross-Linking Amino Acids Peptide sequence lcsh:QH301-705.5 Crystallography biology Organic Compounds Chemistry Lactoferrin Physics Condensed Matter Physics Recombinant Proteins Bacterial Pathogens Molecular Docking Simulation Medical Microbiology Physical Sciences Crystal Structure Pathogens Cellular Structures and Organelles Basic Amino Acids Neisseria Research Article Protein Binding lcsh:Immunologic diseases. Allergy Iron Immunology Research and Analysis Methods Microbiology Transferrin-Binding Protein B 03 medical and health sciences Bacterial Proteins Virology Genetics Solid State Physics Amino Acid Sequence Microbial Pathogens Molecular Biology Chemical Characterization Bacteria Chemical Bonding Lysine Binding protein Organic Chemistry Organisms Chemical Compounds Biology and Life Sciences Membrane Proteins Proteins Cell Biology Outer Membrane Proteins Interferometry 030104 developmental biology lcsh:Biology (General) Docking (molecular) Mutagenesis Site-Directed biology.protein Parasitology Protein G Peptides Carrier Proteins lcsh:RC581-607 |
| Zdroj: | PLoS Pathogens, Vol 13, Iss 3, p e1006244 (2017) PLoS Pathogens |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | 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. Author summary Bacteria responsible for important infections in humans and food production animals survive and proliferate within their host by ‘hijacking’ iron from the host iron-binding proteins, transferrin and lactoferrin. The iron-hijacking process is mediated by a set of surface receptors that are specific for transferrin and lactoferrin from the host. In this study we focused on the receptors from important human pathogens responsible for meningitis and gonorrhea that are being targeted for development of vaccines, thus a detailed understanding of the structure and function of these proteins is needed to aid in vaccine design. Although there is detailed information available for the transferrin receptor proteins, currently information is lacking for the lactoferrin receptor proteins. This study focuses on a specific constituent of the lactoferrin receptor, lactoferrin binding protein B, that also serves to protect the bacteria against host defense mechanisms mediated by small peptides that kill microbes, including ones derived from host lactoferrin. We demonstrated that lactoferrin binding protein B has two different sites for binding lactoferrin, one associated with obtaining iron, the other related to protection against the antimicrobial peptides. This information enabled us to understand how this protein can effectively serve both roles and adapt to the local conditions. |
| Databáze: | OpenAIRE |
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