Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis
| Autor: | Srinivas Chakravarthy, Srinivas Govindan, Andrew D. Mesecar, Ravi Yadav, Nicholas Noinaj, Courtney M. Daczkowski |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
Science Structural Biology and Molecular Biophysics Antimicrobial peptides Mutagenesis (molecular biology technique) lactoferrin binding protein b Peptide Neisseria meningitidis General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound antimicrobial peptides Immune system Bacterial Proteins iron scavenging Lactoferricin multidrug resistance Biology (General) chemistry.chemical_classification Microbiology and Infectious Disease General Immunology and Microbiology biology Chemistry Lactoferrin General Neuroscience Binding protein Mutagenesis food and beverages Transporter General Medicine biology.organism_classification Neisseria gonorrhoeae Cell biology lactoferrin Structural biology biology.protein Medicine Neisseria Other Carrier Proteins Protein Binding Research Article |
| Zdroj: | eLife eLife, Vol 10 (2021) |
| ISSN: | 2050-084X |
| Popis: | Lactoferrin-binding protein B (LbpB) is a lipoprotein present on the surface of Neisseria that has been postulated to serve dual functions during pathogenesis in both iron acquisition from lactoferrin (Lf), and in providing protection against the cationic antimicrobial peptide lactoferricin (Lfcn). While previous studies support a dual role for LbpB, exactly how these ligands interact with LbpB has remained unknown. Here, we present the structures of LbpB from N. meningitidis and N. gonorrhoeae in complex with human holo-Lf, forming a 1:1 complex and confirmed by size-exclusion chromatography small-angle X-ray scattering. LbpB consists of N- and C-lobes with the N-lobe interacting extensively with the C-lobe of Lf. Our structures provide insight into LbpB’s preference towards holo-Lf, and our mutagenesis and binding studies show that Lf and Lfcn bind independently. Our studies provide the molecular details for how LbpB serves to capture and preserve Lf in an iron-bound state for delivery to the membrane transporter LbpA for iron piracy, and as an antimicrobial peptide sink to evade host immune defenses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|