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-Structure paper
Title | Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis. |
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Journal, issue, pages | Elife, Vol. 10, Year 2021 |
Publish date | Nov 9, 2021 |
Authors | Ravi Yadav / Srinivas Govindan / Courtney Daczkowski / Andrew Mesecar / Srinivas Chakravarthy / Nicholas Noinaj / |
PubMed Abstract | Lactoferrin-binding protein B (LbpB) is a lipoprotein present on the surface of that has been postulated to serve dual functions during pathogenesis in both iron acquisition from lactoferrin (Lf), ...Lactoferrin-binding protein B (LbpB) is a lipoprotein present on the surface of 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 and 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. |
External links | Elife / PubMed:34751649 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.85 - 3.7 Å |
Structure data | EMDB-24233, PDB-7n88: PDB-7jrd: |
Chemicals | ChemComp-SO4: ChemComp-FE: ChemComp-BCT: ChemComp-HOH: |
Source |
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Keywords | METAL TRANSPORT / Lactoferrin binding protein B / Neisseria / iron scavenging / lactoferrin / TRANSPORT PROTEIN / MEMBRANE PROTEIN/TRANSPORT PROTEIN / lipoprotein / iron import / MEMBRANE PROTEIN / MEMBRANE PROTEIN-TRANSPORT PROTEIN complex |