A novel insight into the oxidoreductase activity of Helicobacter pylori HP0231 protein.

PLoS One. 2012;7(10):e46563.

Roszczenko P, Radomska KA, Wywial E, Collet JF, Jagusztyn-Krynicka EK.

Department of Bacterial Genetics, Institute of Microbiology, the University of Warsaw, Warsaw, Poland.


BACKGROUND: The formation of a disulfide bond between two cysteine residues stabilizes protein structure. Although we now have a good understanding of the Escherichia coli disulfide formation system, the machineries at work in other bacteria, including pathogens, are poorly characterized. Thus, the objective of this work was to improve our understanding of the disulfide formation machinery of Helicobacter pylori, a leading cause of ulcers and a risk factor for stomach cancer worldwide.

METHODS AND RESULTS: The protein HP0231 from H. pylori, a structural counterpart of E. coli DsbG, is the focus of this research. Its function was clarified by using a combination of biochemical, microbiological and genetic approaches. In particular, we determined the biochemical properties of HP0231 as well as its redox state in H. pylori cells.

CONCLUSION: Altogether our results show that HP0231 is an oxidoreductase that catalyzes disulfide bond formation in the periplasm. We propose to call it HpDsbA.

PMID: 23056345



Dsb proteins control the formation and rearrangement of disulfide bonds during the folding of membrane and exported proteins . The formation of disulfide bonds (Dsb) between cysteine residues stabilizes protein structure, and hence, plays key role in bacterial virulence . Up to date, some Dsb systems have already been elucidated but many more have yet to be unraveled, in particular, the Dsb system in H. pylori, which is a leading cause of ulcers and a risk factor for stomach cancer worldwide.

Our  work led to the characterization of the HP0231, a first dimeric oxidoreductase functioning in an oxidizing pathway. HP0231 acts as periplasmic oxidase, as EcDsbA, despite its structural resemblance to EcDsbG]. HP0231 is a dimeric protein as confirmed by in vitro assay, whereas all DsbAs analyzed to date are monomeric proteins. However, the characteristic motifs of HP0231 are identical to that of EcDsbA (CPHC/VcP) but different from that of EcDsbG (CPYC/TcP).

Dsb system plays an important role in H. pylori pathogenesis. We previously demonstrated that  H. pylori mutant impaired in disulfide bond formation revealed greatly reduced ability to colonize mice gastric mucosa. The emergence and spread of pathogenic bacteria resistant to many antibiotics (multidrug- resistant strains)  have created the need for the development of novel therapeutic agents.  As H. pylori Dsb proteins  are distinct from the Dsb proteins present in other bacterial proteomes and they are involved in a post-translational modification of some H. pylori virulence factors (unpublished data) their characterization may facilitate a future discovery of an effective anti-Helicobacter drug.

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