Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis
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)....
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:0388a112fc7f44eaa9ea04966a3de0cb2021-11-09T14:09:39ZStructural insight into the dual function of LbpB in mediating Neisserial pathogenesis10.7554/eLife.716832050-084Xe71683https://doaj.org/article/0388a112fc7f44eaa9ea04966a3de0cb2021-11-01T00:00:00Zhttps://elifesciences.org/articles/71683https://doaj.org/toc/2050-084XLactoferrin-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.Ravi YadavSrinivas GovindanCourtney DaczkowskiAndrew MesecarSrinivas ChakravarthyNicholas NoinajeLife Sciences Publications LtdarticleNeisserialactoferrin binding protein biron scavengingantimicrobial peptidesmultidrug resistancelactoferrinMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Neisseria lactoferrin binding protein b iron scavenging antimicrobial peptides multidrug resistance lactoferrin Medicine R Science Q Biology (General) QH301-705.5 |
| spellingShingle |
Neisseria lactoferrin binding protein b iron scavenging antimicrobial peptides multidrug resistance lactoferrin Medicine R Science Q Biology (General) QH301-705.5 Ravi Yadav Srinivas Govindan Courtney Daczkowski Andrew Mesecar Srinivas Chakravarthy Nicholas Noinaj Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis |
| description |
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. |
| format |
article |
| author |
Ravi Yadav Srinivas Govindan Courtney Daczkowski Andrew Mesecar Srinivas Chakravarthy Nicholas Noinaj |
| author_facet |
Ravi Yadav Srinivas Govindan Courtney Daczkowski Andrew Mesecar Srinivas Chakravarthy Nicholas Noinaj |
| author_sort |
Ravi Yadav |
| title |
Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis |
| title_short |
Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis |
| title_full |
Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis |
| title_fullStr |
Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis |
| title_full_unstemmed |
Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis |
| title_sort |
structural insight into the dual function of lbpb in mediating neisserial pathogenesis |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/0388a112fc7f44eaa9ea04966a3de0cb |
| work_keys_str_mv |
AT raviyadav structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT srinivasgovindan structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT courtneydaczkowski structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT andrewmesecar structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT srinivaschakravarthy structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT nicholasnoinaj structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis |
| _version_ |
1718440900908023808 |