Ferritins are recognized as key players in the
iron storage and detoxification processes.
Iron acquisition in the case of pathogenic bacteria has long been established as an important virulence mechanism. Here, we report a 3.0 Å crystal structure of a
ferritin, annotated as
Bacterioferritin B (BfrB), from Mycobacterium tuberculosis (Mtb), the causative agent of
tuberculosis that continues to be one of the world's deadliest diseases. Similar to the other members of
ferritin family, the Mtb BfrB subunit exhibits the characteristic fold of a four-helical bundle that possesses the
ferroxidase catalytic centre. We compare the structure of Mtb BfrB with representatives of the
ferritin family belonging to the archaea, eubacteria and eukarya. Unlike most other
ferritins, Mtb BfrB has an extended C-terminus. To dissect the role of this extended C-terminus, truncated Mtb BfrB was purified and biochemical studies implicate this region in
ferroxidase activity and
iron release in addition to providing stability to the
protein. Functionally important regions in a
protein of known 3D-structure can be determined by estimating the degree of conservation of the
amino-acid sites with its close homologues. Based on the comparative studies, we identify the slowly evolving conserved sites as well as the rapidly evolving variable sites and analyze their role in relation to structure and function of Mtb BfrB. Further, electrostatic computations demonstrate that although the electrostatic environment of catalytic residues is preserved within the family, extensive variability is exhibited by residues defining the channels and pores, in all likelihood keeping up with the diverse functions executed by these
ferritins in varied environments.