Document Type

Article

Publication Date

12-11-2012

Abstract

Bacterioferritin (Bfr) is a spherical protein composed of 24 subunits and 12 heme molecules. Bfrs contribute to regulate iron homeostasis in bacteria by capturing soluble but potentially toxic Fe2+ and by compartmentalizing it in the form of a bioavailable ferric mineral inside the protein's hollow cavity. When iron is needed, Fe3+ is reduced and mobilized into the cytosol as Fe2+. Hence, key to the function of Bfr is its ability to permeate iron ions in and out of its interior cavity, which is likely imparted by a flexible protein shell. To examine the conformational flexibility of Bfrs in a native-like environment and the way in which the protein shell interacts with monovalent cations, we have performed molecular dynamics (MD) simulations of BfrB from Pseudomonas aeruginosa (Pa BfrB) in K2HPO4 solutions at different ionic strengths. The results indicate the presence of coupled thermal fluctuations (dynamics) in the 4-fold pores and B-pores of the protein, which is key to allowing passage of monovalent cations through the protein shell using B-pores as conduits. The MD simulations also show that Pa BfrB ferroxidase centers are highly dynamic and permanently populated by transient cations exchanging with other cations in the interior cavity, as well as the solution bathing the protein. Taken together, the findings suggest that Fe2+ passes across the Pa BfrB shell via B-pores and that the ferroxidase pores allow the capture and oxidation of Fe2+, followed by translocation of Fe3+ to the interior cavity, aided by the conformationally active H130. © 2012 American Chemical Society.

Publication Source (Journal or Book title)

Biochemistry

First Page

9900

Last Page

9910

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