Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Lactoferrin-binding protein B (LbpB) is a surface lipoprotein in Neisseria species.
• LbpB is hypothesized to mediate iron acquisition from lactoferrin (Lf) and provide resistance to lactoferricin (Lfcn).
• The precise molecular mechanisms of LbpB interaction with Lf and Lfcn remain unelucidated.

Purpose of the Study:

• To determine the structural basis of LbpB interaction with human lactoferrin (Lf).
• To elucidate the molecular mechanisms underlying LbpB's dual roles in iron acquisition and antimicrobial peptide resistance.
• To investigate the independent binding of Lf and Lfcn to LbpB.

Main Methods:

• X-ray crystallography was used to determine the structures of LbpB from N. meningitidis and N. gonorrhoeae in complex with holo-Lf.
• Size-exclusion chromatography and small-angle X-ray scattering confirmed the 1:1 complex formation.
• Mutagenesis and binding studies were performed to analyze Lf and Lfcn interactions.

Main Results:

• The structures reveal a 1:1 complex between LbpB and holo-Lf, with extensive interaction between LbpB's N-lobe and Lf's C-lobe.
• LbpB exhibits a preference for holo-Lf.
• Mutagenesis and binding data indicate that Lf and Lfcn bind to LbpB independently.

Conclusions:

• LbpB captures iron-bound Lf for subsequent iron delivery to the LbpA transporter, facilitating bacterial iron piracy.
• LbpB acts as a molecular sink for Lfcn, protecting Neisseria from host immune defenses.
• These findings provide molecular insights into LbpB's crucial roles in Neisseria pathogenesis.