Date Published: August 1, 2019
Publisher: Public Library of Science
Author(s): Christoph Howe, Vamsi K. Moparthi, Felix M. Ho, Karina Persson, Karin Stensjö, Inês A. Cardoso Pereira.
Dps proteins (DNA-binding proteins from starved cells) have been found to detoxify H2O2. At their catalytic centers, the ferroxidase center (FOC), Dps proteins utilize Fe2+ to reduce H2O2 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 Fe2+ utilizing O2, but no evidence for its use of the oxidant H2O2 could be found. We identified Zn2+ to be an effective inhibitor of the O2-mediated Fe2+ 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.
Dps proteins (DNA-binding proteins from starved cells), also referred to as miniferritins, are only found in prokaryotes and belong to the class of ferritin-like proteins , alongside with bacterioferritins (bfr) and ferritins (ftn). Dps proteins exhibit a remarkable three-dimensional structure consisting of twelve monomers (or six dimers), forming a spherically shaped protein complex with a hollow spherical interior [2,3].
In this study we have gathered structural and biochemical data that supports our previously proposed hypothesis that the NpDps4 is an atypical Dps protein. NpDps4 diverges from canonical Dps especially by its amino acid composition at the FOC. Also, no evidence for NpDps4 using H2O2 as an oxidant in the presence of O2 was discovered.