Pathogenic bacteria in the family Neisseriaceae express surface receptors to acquire iron from the mammalian iron-binding proteins. Transferrins and lactoferrins constitute a family of iron-binding proteins highly related in both sequence and structure, yet the bacterial receptors are able to distinguish between these proteins and uphold a strict binding specificity. In order to understand the molecular basis for this specificity, the interaction between human lactoferrin (hLf) and the lactoferrin-binding protein A (LbpA) from Moraxella catarrhalis was studied. A periplasmic expression system was designed for the heterologous expression of LbpA, which enabled the investigation of its binding activity in the absence of lactoferrin-binding protein B (LbpB). To facilitate delineation of the LbpA-binding regions of hLf, chimeric proteins composed of hLf and bovine transferrin were made. Binding studies performed with the chimeric proteins and recombinant LbpA identified two binding regions within the C-terminus of hLf. Furthermore, native LbpA from Moraxella and Neisseria spp. bound the identical spectrum of hybrid proteins as the recombinant receptor, demonstrating a conserved binding interaction with the C-lobe of hLf.
Crystal Structure ofPasteurella haemolyticaFerric Ion-binding Protein A Reveals a Novel Class of Bacterial Iron-binding Proteins
