Dps Functions as a Key Player in Bacterial Iron Homeostasis

Abstract

Iron plays a vital role in the maintenance of life, being central to various cellular processes, from respiration to gene regulation. It is essential for iron to be stored in a nontoxic and readily available form. DNA binding proteins under starvation (Dps) belong to the ferritin family of iron storage proteins and are adept at storing iron in their hollow protein shells. Existing solely in prokaryotes, these proteins have the additional functions of DNA binding and protection from oxidative stress. Iron storage proteins play a functional role in storage, release, and transfer of iron and therefore are central to the optimal functioning of iron homeostasis. Here we review the multifarious properties of Dps through relevant biochemical and structural studies with a focus on iron storage and ferroxidation. We also examine the role of Dps as a possible candidate as an iron donor to iron-sulfur (Fe-S) clusters, which are ubiquitous to many biological processes.

Figure 1

X-ray structures of E. coli (A) Dps in green (PDB ID: 1dps), ferritin in light blue (PDB ID: 1eum), and bacterioferritin in red (PDB ID: 3e1j). (B) Cross-sectional views showing the central cavity available for iron storage. Ferritins and bacterioferritins have a capacity of around 4500 iron atoms per molecule, whereas the smaller Dps shell has a capacity of around 500 iron atoms.

Figure 2

(A) Top panel: X-ray structure of E. coli ferritin monomer (PDB ID: 1eum) showing a typical ferritin-fold characterized by a four helical bundle, made up of two homologous pairs of antiparallel alpha helices arranged in an up–down–down–up topology. The intrasubunit ferroxidation site is indicated with a dashed black circle, and the expanded image is shown to the right. Fe ions are in orange. The color coding of the helices from A–E is as in the labels. Bottom panel: X-ray structure of Rhodospirillum rubrum encapsulated ferritin (PDB ID: 5DA5) showing a dimer formed of two monomeric subunits of antiparallel alpha helices, color coded A–C as indicated in the label. The ferroxidation sites (one per monomer) are in dashed circles, zoomed in on the rectangle on the left. (B) Top view of the EncFtn pentamer of dimer (decamer) arrangement in the top panel and side view in the bottom panel. The decamer is 7 nm in diameter with a thickness of 4.5 nm (PDB ID: 5DA5).

Figure 3

Multimerization interfaces of Dps. A Dps monomer in green color (PDB ID: 1dps) forms three types of symmetry interfaces with its neighboring homomeric subunits, namely, (A) a 2-fold interface and two types of trimeric (3-fold) interfaces, (B) ferritin-like 3-fold interface, and (C) Dps-like trimeric interface.

Figure 4

Structural switch from a 12-mer to a 24-meric assembly. A ferritin-fold is exemplified by a monomer of Dps1 from M. smegmatis (MsDps1) (PDB ID: 1VEI). A single point mutation in the AB loop (in green) from Phe47 (green stick representation) to Glu47 (red stick) (PDB ID: 5H46) switches the assembly to a ferritin-like 24-mer, under crystalline conditions.

Figure 5

View of the internal organization of a typical Dps shell (Dps2 from M.smegmatis, PDB ID: 2z90) showing the iron entry sites (in dashed triangle) and the ferroxidation site (dashed circle). These lie at the interface between different subunits of the dodecamer, which are colored differently to indicate this intricate interplay. A conserved arginine (Arg73 in MsDps2) is thought to link the ferroxidation site to the iron entry site by stabilizing this interface.

Figure 6

DNA protection by Dps involves a direct mode by physical binding and condensation of DNA, protecting it from the onslaught of deleterious agents. An indirect mode of action is through the sequestration of free iron, preventing the generation of reactive oxygen species (ROS) by the Fenton reaction.

Figure 7

Role of Dps in Fe–S cluster protein maintenance. The Fe–S cluster protein is denoted by a brown oval with holo [Fe–S] and apo forms. Dps is shown as a green sphere and could be involved in donating iron to the biosynthesis\repair pathways. It also prevents the Fenton-mediated generation of ROS and prevents oxidative damage to the cluster.