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)....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/71683 |
| _version_ | 1811200793435439104 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:09:41Z |
| format | Article |
| id | doaj.art-0388a112fc7f44eaa9ea04966a3de0cb |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:09:41Z |
| publishDate | 2021-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0388a112fc7f44eaa9ea04966a3de0cb2022-12-22T03:52:26ZengeLife Sciences Publications LtdeLife2050-084X2021-11-011010.7554/eLife.71683Structural insight into the dual function of LbpB in mediating Neisserial pathogenesisRavi Yadav0https://orcid.org/0000-0003-2879-0465Srinivas Govindan1https://orcid.org/0000-0002-0414-7822Courtney Daczkowski2Andrew Mesecar3Srinivas Chakravarthy4Nicholas Noinaj5https://orcid.org/0000-0001-6361-2336Purdue University Interdisciplinary Life Sciences Program, West Lafayette, United States; Department of Biological Sciences,Purdue University, West Lafayette, United StatesWeldon School of BiomedicalEngineering, Purdue University, West Lafayette, United StatesDepartment of Biochemistry, Purdue University, West Lafayette, United StatesDepartment of Biological Sciences,Purdue University, West Lafayette, United States; Department of Biochemistry, Purdue University, West Lafayette, United StatesBIO-CAT, Illinois12 Institute of Technology, Lemont, United StatesDepartment of Biological Sciences,Purdue University, West Lafayette, United States; Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, United StatesLactoferrin-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.https://elifesciences.org/articles/71683Neisserialactoferrin binding protein biron scavengingantimicrobial peptidesmultidrug resistancelactoferrin |
| spellingShingle | Ravi Yadav Srinivas Govindan Courtney Daczkowski Andrew Mesecar Srinivas Chakravarthy Nicholas Noinaj Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis eLife Neisseria lactoferrin binding protein b iron scavenging antimicrobial peptides multidrug resistance lactoferrin |
| title | 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_short | 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 |
| topic | Neisseria lactoferrin binding protein b iron scavenging antimicrobial peptides multidrug resistance lactoferrin |
| url | https://elifesciences.org/articles/71683 |
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