Ferric-binding protein

The determination of the structure of the iron transporter, ferric-binding, protein (hFBP)t from Haemophilus influenzae (Bruns et ah, 1997) at 0.16 nm resolution shows that it is a member of the transferrin superfamily, which includes both the transferrins and a number of periplasmic binding proteins (PBP). The PBPs transport a wide variety of nutrients, including sugars, amino acids and ions, across the periplasm from the outer to the inner (plasma) membrane in bacteria (see Chapter 3). Iron binding by transferrins (see below) requires concomitant binding of a carbonate anion, which is located at the N-terminus of a helix. This corresponds to the site at which the anions are specifically bound in the bacterial periplasmic sulfate- and... 

Figure 11.1 Schematic representation of iron uptake mechanisms, (a) The transferrin-mediated pathway in animals involves receptor-mediated endocytosis of diferric transferrin (Tf), release of iron at the lower pH of the endocytic vesicle and recycling of apoTf. (b) The mechanism in H. influenzae involves extraction of iron from Tf at outer membrane receptors and transport to the inner membrane permease system by a periplasmic ferric binding protein (Fbp). From Baker, 1997. Reproduced by permission of Nature Publishing Group.

As noted in Section 3, some pathogenic bacteria have transferrin receptors on their outer membranes to acquire diferric transferrin from their host. These outer membrane receptors extract the iron from the transferrin and transport it into the periplasm where it is picked up by the periplasmic ferric binding proteins (Fbp), which carry the iron to a transmembrane protein in the inner membrane that conveys it into the cytoplasm. A considerable amount of chemical and structural information has been gathered for Fbp, which is sometimes referred to as bacterial transferrin in recognition of its similarities with animal transferrin. ... 

For example, the kinetics of Fe dissociation from Fe +nFbp(X) (nFbp = recombinant ferric binding protein from Neisseria meningitides, X = citrate) driven... 

Figure 2.1 Schematic representation of the OTTLE cell and representative spectra obtained in a spectroelectrochemistry experiment involving ferric-binding protein (top insert) and myoglobin (bottom insert).

Not only do TV. meningitidis and H. influenzae scavenge iron from host transferrin but they also have transferrin-like iron transport proteins in their periplasms which have been named Ferric Binding Proteins (Fbps). We shall consider animal transferrins separately from Fbps because despite their evident similarities, there are distinct chemical differences between them. 

For example, the kinetics of Fe dissociation from Fe +nFbp(X) (nFbp = recombinant ferric binding protein from Neisseria meningitides, X = P04, citrate) driven by H+ were studied by pH-Jump stopped-flow methods. Researchers used this technique to induce Fe + dissociation from Fe + nFbp(X) (X = P04, citrate), which enabled researchers to study the mechanism in the absence of... 

Fe Release from Ferric-binding Protein in Gram-negative Bacteria... 

The transferrin (Tf) family of proteins contains five members serum transferrin, lactoferrin, ovotransferrin, melanotransferrin (also called p97), and the ferric-binding protein found in Gram-negative bacteria (Table i),121-126... 

Ferric Binding Protein Gram-negative bacteria Glu, 2 Tyr, His, phosphate, water 1 148... 

The ferric-binding protein (Fbp) found in pathogenic Gram-negative bacteria shuttles the iron scavenged from the host transferrin or lactoferrin across the peiiplasmic space to the CM of the bacterium. " Fbp binds ferric ion (affinity constant of 10 M ) almost as strongly as transferrin... 

Figure 15 Transferrin-mediated iron uptake by bacteria. One lobe of ferric transferrin binds to the OM transmembrane receptor protein TbpA TbpB facilitates bmdmg.The unchelated ferric ion passes through the membrane and is then bound by the ferric-binding protein (FbpA), located in the periplasm. A TonB-ExbBD-like protein system provides the energy required for this process. FbpA shuttles the iron to the CM transmembrane protein FbpB. The iron moves into the cytoplasm following hydrolysis of ATP by FbpC.

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