The Dps4 from Nostoc punctiforme ATCC 29133 is a member of His-type FOC containing Dps protein class that can be broadly found among cyanobacteria

Abstract

Dps proteins (DNA-binding proteins from starved cells) have been found to detoxify H 2 O 2 . At their catalytic centers, the ferroxidase center (FOC), Dps proteins utilize Fe 2+ to reduce H 2 O 2 and therefore play an essential role in the protection against oxidative stress and maintaining iron homeostasis. Whereas most bacteria accommodate one or two Dps, there are five different Dps proteins in Nostoc punctiforme , a phototrophic and filamentous cyanobacterium. This uncommonly high number of Dps proteins implies a sophisticated machinery for maintaining complex iron homeostasis and for protection against oxidative stress. Functional analyses and structural information on cyanobacterial Dps proteins are rare, but essential for understanding the function of each of the NpDps proteins. In this study, we present the crystal structure of NpDps4 in its metal-free, iron- and zinc-bound forms. The FOC coordinates either two iron atoms or one zinc atom. Spectroscopic analyses revealed that NpDps4 could oxidize Fe 2+ utilizing O 2 , but no evidence for its use of the oxidant H 2 O 2 could be found. We identified Zn 2+ to be an effective inhibitor of the O 2 -mediated Fe 2+ oxidation in NpDps4. NpDps4 exhibits a FOC that is very different from canonical Dps, but structurally similar to the atypical one from DpsA of Thermosynechococcus elongatus . Sequence comparisons among Dps protein homologs to NpDps4 within the cyanobacterial phylum led us to classify a novel FOC class: the His-type FOC. The features of this special FOC have not been identified in Dps proteins from other bacterial phyla and it might be unique to cyanobacterial Dps proteins.

Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle

“…The protein Dps4 from Nostoc punctiforme (NpDps4) (PDB ID code 5hjf) ( 41 ) meets all the above criteria ( Fig. 2 B ).…”

Biochemical and structural characterization of a thermostable Dps protein with His‐type ferroxidase centers and outer metal‐binding sites

“…Compared with the sequences of conventional Dps proteins, TlDps1 possesses unique amino acids including Phe52, His78, and His164, which are characteristic of Dps proteins with His-type FOCs as previously isolated from the cyanobacteria T. elongatus and N. punctiforme [6,7]. A sequence similarity search illustrated that TlDps1 shares 66% and 70% sequence identity with the His-type FOC-containing proteins TeDpsA and NpDps4, respectively, whereas it shares low sequence identities with conventional Dps proteins from bacteria such as Escherichia coli (EcDps, 27%), Listeria innocua (LiDps, 27%), Mycobacterium smegmatis (MsDps1, 28%), Deinococcus radiodurans (DrDps1, 28%), and T. elongatus (TeDps, 30%).…”

“…FOCs catalyze the oxidative conversion of Fe 2+ to Fe 3+ using O 2 and/or H 2 O 2 to protect DNA from oxidative damage caused by the Fenton reaction, and Dps proteins take up Fe cations within the cavity through pores [5]. Because FOCs have a crucial role in cell survival under oxidative stresses, the DNA-binding and iron uptake ability of Dps proteins together with crystal structures of FOCs from various types of bacteria have been revealed [3,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Conventional FOCs in Dps proteins consist of highly conserved amino acids, including two His, one Trp, one Asp, and one Glu residue, and two Fe cations are coordinated to these amino acid residues.…”

Bacterial iron detoxification at the molecular level

“…The ligation of the ferroxidase center in this protein differs markedly from canonical Dps proteins and closely resembles that of bacterial Bfrs discussed above ( 191 ). Finally, NpDps4 possesses unusually His-rich ligation of iron at the ferroxidase center and utilizes only O 2 and not H 2 O 2 as an oxidant for iron ( 198 ). Accordingly, a role for this protein has been proposed as an O 2 scavenger within heterocysts where nitrogenase activity requires that a microoxic (<10 μ m O 2 ) environment be maintained ( 199 ).…”

“…Accordingly, a role for this protein has been proposed as an O 2 scavenger within heterocysts where nitrogenase activity requires that a microoxic (<10 μ m O 2 ) environment be maintained ( 199 ). Based on sequence comparisons with other Dps proteins, it has been suggested that this type of reaction center, which is common among, but restricted to, the cyanobacteria ( 198 ) be classified as the His-type ferroxidase center.…”