Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis
- Purdue Univ. Interdisciplinary Life Sciences Program, West Lafayette, IN (United States); Purdue Univ., West Lafayette, IN (United States)
- Purdue Univ., West Lafayette, IN (United States)
- Illinois12 Inst. of Technology, Lemont, IL (United States)
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.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- Grant/Contract Number:
- AC02-06CH11357
- OSTI ID:
- 1841206
- Journal Information:
- eLife, Vol. 10; ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.Copyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
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