Cargando…
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)....
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577839/ https://www.ncbi.nlm.nih.gov/pubmed/34751649 http://dx.doi.org/10.7554/eLife.71683 |
_version_ | 1784596144667492352 |
---|---|
author | Yadav, Ravi Govindan, Srinivas Daczkowski, Courtney Mesecar, Andrew Chakravarthy, Srinivas Noinaj, Nicholas |
author_facet | Yadav, Ravi Govindan, Srinivas Daczkowski, Courtney Mesecar, Andrew Chakravarthy, Srinivas Noinaj, Nicholas |
author_sort | Yadav, Ravi |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8577839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-85778392021-11-12 Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis Yadav, Ravi Govindan, Srinivas Daczkowski, Courtney Mesecar, Andrew Chakravarthy, Srinivas Noinaj, Nicholas eLife Microbiology and Infectious Disease 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. eLife Sciences Publications, Ltd 2021-11-09 /pmc/articles/PMC8577839/ /pubmed/34751649 http://dx.doi.org/10.7554/eLife.71683 Text en © 2021, Yadav et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Microbiology and Infectious Disease Yadav, Ravi Govindan, Srinivas Daczkowski, Courtney Mesecar, Andrew Chakravarthy, Srinivas Noinaj, Nicholas Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis |
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 | Microbiology and Infectious Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577839/ https://www.ncbi.nlm.nih.gov/pubmed/34751649 http://dx.doi.org/10.7554/eLife.71683 |
work_keys_str_mv | AT yadavravi structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT govindansrinivas structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT daczkowskicourtney structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT mesecarandrew structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT chakravarthysrinivas structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis AT noinajnicholas structuralinsightintothedualfunctionoflbpbinmediatingneisserialpathogenesis |