DpsC Protein (PDB ID: 4CYB) from Streptomyces Coelicolor

Created by Sung Lee

            DpsC protein from Streptomyces coelicolor (4CYB) is one of the three Dps-like proteins, which is a type of iron binding proteins, the virus encodes along with DpsA and DpsB. Dps proteins can oxidize and deposit iron in the form of ferric oxide. Ferric oxide, associated ligand of DpsC, acts as a vessel for the formation and storage of a bioavailable iron oxide core. DpsC is also able to bind DNA and protect them from potentially fatal effects of redox form of irons such as Fe(II) or Fe(III) [1].

           Each subunits of DpsC contains five α-helices and two β-strands. Because it contains of twelve subunits totally, DpsC contains sixty 

α-helices and twenty-four 

β-strands as its secondary structure. Moreover, they are responsible for the establishment of the inner-subunit ferroxidase center along with the six dimer interfaces. The molecular weight of DspC is 22517.56 Da, and its isoelectric point (pI) is 5.73 [2].

            The monomer of DpsC consists of the archetypal ferritin four-helix bundle (A, B, C, and D helices) with an additional short helix (BC). Those four-helix bundles arrange themselves to remain antiparallel. It assembles its twelve subunits into small nanocages to conserve ferroxidase center at the interface between two antiparallel subunits that form the twofold symmetry dimers. As a result, the multimeric assembly of DpsC has twofold symmetry axis and two sets of threefold symmetry axis so that each subunit interface with five other subunits [1].

            Some of residues in DpsC have important functions. Arg-28 forms two hydrogen bonds and a salt bridge with Glu-135 so that the N-terminal tail extends across its partner in the dimer and is anchored in place across the surface of the dodecamer to stabilize the structures. Ile-30 interfaces with a total of five amino acids and provide a method for correctly positioning the tail in place on the surface of the dodecamer allowing other vital interactions to occur. Seven of the eight residues in the C-terminal tail of DpsC interface with 18 interfacing residues; hydrogen bond between His-199 and Ser-141 pin the tail to the surface of the threefold symmetry-related subunits. Gln-83 takes part in a three-partite interface with His-199 and Ser-141 to give stability of the Dps-like trimer [1].

            The clear distinctions of DpsC from Streptomyces coelicolor from other Dps-like proteins are the length and the functions of its terminal extensions or tails at N and C termini. Although most Dps proteins possess this terminal extensions at their N and C termini, depending on the organisms encode the Dps proteins and on the existence of their terminal extensions, Dps proteins have different functions. For example, removal of the N-terminal tail in E. coli Dps abolishes DNA binding [8], while a tail-deleted mutant of Dps from L. lactis (1ZUJ) does not give much effect on its original function [6]. The removal of C-tail from DrDps2 (2C2J) encoded by D. radiodurans  result in loss of the ability to assemble into a dimer [7]. Even DpsA from Streptomyces coelicolor shows the different functions based on the existence of tails. The removal of the C-tail affects oligomerization partially. However, the removal of the N-tail abolishes high-order oligomerization beyond dimer complexes. DpsC proteins have relatively long N-terminal tails and short C-tails. 44 residue-long N-terminal tail is heavily involved in the dimer and ferritin-like interface by contributing to their stability while 7 out of 8 residues in the C-terminal tail contribute to important interfaces. Each tail braces its adjacent subunits in the Dps-like trimer interface, reinforcing it [1].

            PSI-BLAST was used to find a comparison protein based on primary structure  while Dali server was used to find a comparison protein based on tertiary structure. If E value of comparison protein structure is less than 0.5, the primary structure of comparison protein is similar with that of protein of interest significantly. On the other hand, if Z score is above 2, tertiary structure of comparison protein is similar with that of protein of interest significantly. DIP-2 from Bacillus Authracis (1JIG), based on data from Dali server, has 21.5 as its Z score and exhibits 24% similarity on tertiary structures [3].  The protein also has 8*10^-50 as its E value, which shows considerable similarity on its secondary structure [4]. As the proof, the superimposition between DpsC and DIP-2 shows that large amount of those two proteins' structures overlaps. 

           DIP-2 from Bacillus Authracis is also iron-binding proteins like DpsC; it uses iron(III) ion as its ligand to deposit oxygen as the form of ferric oxide and its twelve subunits surround the ferric oxide. However, it does not have β-strand, and DpsC has sodium ion as additional ligand although its function is still not figured out [1,5].