Lactoferrin binding protein B - a bi-functional bacterial receptor protein.

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Lactoferrin binding protein B (LbpB) is a key outer membrane protein in Neisseria meningitidis and other pathogens.
• LbpB is implicated in bacterial defense against antimicrobial peptides and potentially in iron acquisition.
• Limited structural and biophysical data exist regarding LbpB's interaction with lactoferrin (Lf).

Purpose of the Study:

• To investigate the structural and functional interactions between LbpB and human lactoferrin (hLf).
• To elucidate the role of LbpB in iron acquisition and bacterial defense mechanisms.

Main Methods:

• Utilized crosslinking and deuterium exchange mass spectrometry (DXMS).
• Employed information-driven computational docking and bio-layer interferometry (BLI).
• Performed site-directed mutagenesis to probe LbpB:hLf complexes.

Main Results:

• Confirmed a 1:1 complex formation between iron-loaded Lf and LbpB, involving the Lf C-lobe and LbpB N-lobe, suggesting a role in iron acquisition.
• Identified binding of the Lf N-lobe to negatively charged regions of the LbpB C-lobe, leading to higher-order complex formation.
• Demonstrated that LbpB exhibits dual roles, primarily iron acquisition with iron-loaded Lf and binding apo Lf under inflammatory conditions.

Conclusions:

• LbpB plays a dual role in bacterial pathogenesis, adapting its function based on lactoferrin availability and iron load.
• The interaction of LbpB with Lf is crucial for both iron acquisition and bacterial survival in diverse host environments.
• Further structural and biophysical characterization of LbpB:Lf complexes can inform therapeutic strategies against Gram-negative pathogens.