bi3013388_si_006.mpg (1.54 MB)
Protein Dynamics and Ion Traffic in Bacterioferritin
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posted on 2012-12-11, 00:00 authored by Huan Rui, Mario Rivera, Wonpil ImBacterioferritin (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.