Miniferritins: Small multifunctional protein cages

The subject of this review article was first reported approximately three decades ago upon the discovery of a starvation-inducible protein found tightly bound to chromosomal DNA in 3-day-old starved cultures of Escherichia coli. As a result, they were named “DNA-binding protein from starved cells” or Dps. Recognized by their homology to ferritins, these proteins were classified as a new branch of the Ferritin-like proteins superfamily and designated as miniferritins. These proteins present a cage-like structure built by twelve identical four-helix bundle monomers. They are capable of performing fast oxidation of ferrous ions using hydrogen peroxide, while still retaining the possibility of using molecular oxygen as co-substrate, and subsequently accumulating ferric ions in its cavity in a ferric mineral form. This complex catalytic activity is designed to protect cells from oxidative stress conditions, reducing the risk of harmful oxygen radical species being formed in particular physiological conditions. They are also capable of binding to and compacting DNA, becoming the most abundant nucleoid protein in the stationary phase, adding physical protection to the chemical protection attained by the ferroxidation reaction. Miniferritins are almost ubiquitous to Bacteria and Archaea, with protein characterization reported for over 60 microorganisms and several thousands of homologous genes annotated in current genomic databases, which demonstrates the importance of these proteins in Prokarya. In this manuscript we offer an extensive, yet concise, description of the state of the art on miniferritins, including their regulation, the global structural features, metal center characterization, diverse functional properties and the current stage of multifaceted biotechnological applications.