Motions connecting pores and catalytic sites enable bacterioferritin function and iron traffic
Two types of iron storage proteins, ferritin (Ftn) and bacterioferritin (Bfr), play major roles in maintaining bacterial iron homeostasis to prevent iron-induced cell toxicity. The roles played by Ftn and Bfr on the fitness and virulence of pathogenic bacteria are just beginning to emerge. Bfrs are unique to bacteria, and significant recent advances have been made toward understanding their dual function of (i) iron uptake/storage to prevent toxicity and (ii) iron mobilization for incorporation of the nutrient in metabolism. However, many important questions remain unanswered. For example, Bfrs assemble from 24 subunits to form a hollow, spherical architecture, which has eight 3-fold pores, six 4-fold pores, 24 B-pores, and 24 ferroxidase centers. One important question is how the catalytic sites and the pores in the 24-mer assembly communicate to facilitate iron traffic across the Bfr protein shell. To answer this question, the effect of mutations in the 4-fold and B-pores of BfrB from Pseudomonas aeruginosa was investigated. Results obtained from x-ray crystallography, MD simulations and biochemistry show that the site-directed mutations not only exert local influence on the pores, but also influence the distant ferroxidase catalytic centers via networking motions.