Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Poster Session I

23 – POS Board 23 The Iron-oxygen Switch in Anaerobic Bacterium Porphyromonas Gingivalis

Janina Lewis , Cecilia Anaya - Bergman, Sai Yanamandra. Virginia Commonwealth University, Richmond, USA.

Bacterial regulation of oxidative stress response typically includes proteins like SoxRS, PerR and OxyR, while iron uptake mechanisms are regulated by iron-dependent regulators like Fur or DtxR-like proteins. Here we investigated the iron-dependent transcriptome of the anaerobic bacterium Porphyromonas gingivalis. We show that the bacterium regulates both iron uptake and oxidative stress mechanisms utilizing a homolog of the nitrate/peroxide stress regulator OxyR. We present the structure of the protein determined using x-ray crystallography. Transcriptional profiling reveals that the mode of regulation by OxyR is dependent on iron levels present in cell culture. We show that this OxyR protein binds iron, which we hypothesize coordinates the ligand in the redox cysteine 199 (Cys199) site analogous to that of Escherichia coli and Neisseria meningitides OxyR. A Cys199Ser mutation abolishes protein binding to iron as well as DNA and confers a bacterial phenotype like the OxyR deficient strain. Our data support a new mode of OxyR activation in the anaerobe P. gingivalis that depends on iron binding and leads to regulation of both iron uptake and oxidative stress response genes. Based on structural similarity of P. gingivalis and E. coli OxyR’s our model may also shed light on previous modes of OxyR regulation in aerobic bacteria, which involve an oxidative stress induced cysteine switch or cysteine nitrosylation, as such modifications may be metal-catalyzed thus allowing for sensing low levels of peroxide or nitrite in vivo.

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