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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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Autores principales: Yadav, Ravi, Govindan, Srinivas, Daczkowski, Courtney, Mesecar, Andrew, Chakravarthy, Srinivas, Noinaj, Nicholas
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
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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.
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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
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