Bacterioferritin nanocage: Structure, biological function, catalytic mechanism, self-assembly and potential applications

Bacterioferritin (Bfr) is a subfamily of ferritin protein family. Bfrs are composed of 24 identical subunits and self-assemble into 4-3-2-fold symmetric cage-like structure with the incorporation of 12 heme groups into twelve 2-fold symmetric binding sites between subunits. Bfr protein cage has an outer diameter of similar to 12 nm and interior cavity diameter of similar to 8 nm with a total of 62 pores to connect the interior cavity with the bulk solution outside the protein nanocage. In vivo, the interior cavity of Bfr can store up to similar to 2700 iron atoms in the ferrihydrite-like mineral. Recent years, more and more Bfr structures have been solved, which elucidated more details about the ferroxidase center, the catalytic mechanism, the possible channels used by iron ions to access the interior cavity, the electron transfer pathway involved in the iron redox cycle, and the molecular function of the heme group. The preliminary applications of both mammalian and bacterial ferritins in drug delivery, imaging diagnosis, and nanoparticle vaccine make Bfr exploration uniquely attractive for researchers from a broad range of research fields because Bfr has advantages over ferritins in controlling the self-assembly and redesigning the subunit. In this article, we outline the structure of Bfr, review the recent progress in the molecular mechanism of Bfr to store and release iron, and focus on the self-assembly and genetic modification of Bfr nanocage. Based on the comparison between Bfr and other ferritin family members, we further discuss the potential applications of Bfr. We expect that both fundamental and applied researches on Bfr will attract broad interest in protein nanocage design, nanomedicine, precise therapy, nanoparticle vaccine, bionanotechnology, bionanoelectronics, and so on.