Abstract
The medically important human pathogen Helicobacter pylori relies on a collection of highly conserved heat-shock and chaperone proteins to preserve the integrity of cellular polypeptides and to control their homeostasis in response to external stress and changing environmental conditions. Among this set of chaperones, the CbpA protein has been shown to play a regulatory role in heat-shock gene regulation by directly interacting with the master stress-responsive repressor HspR. Apart from this regulatory role, little is known so far about CbpA functional activities. Using biochemistry and molecular biology approaches, we have started the in vitro functional characterization of H. pylori CbpA. Specifically, we show that CbpA is a multifunctional protein, being able to bind DNA and to stimulate the ATPase activity of the major chaperone DnaK. In addition, we report a preliminary observation suggesting that CbpA DNA-binding activity can be affected by the direct interaction with the heat-shock master repressor HspR, supporting the hypothesis of a reciprocal crosstalk between these two proteins. Thus, our work defines novel functions for H. pylori CbpA and stimulates further studies aimed at the comprehension of the complex regulatory interplay among chaperones and heat-shock transcriptional regulators.
Highlights
All living organisms respond to changing external conditions by synthetizing a class of highly conserved proteins whose function is to assist protein folding and to get rid of dangerous cytoplasmic aggregates made of denatured polypeptides
Overexpression of CbpA leads to deregulation of heat-shock response in vivo, supporting the idea that this protein plays a regulatory role in H. pylori heat-shock response [4]
Starting from a primary sequence comparison between H. pylori and E. coli CbpA proteins, we show that H. pylori CbpA has a co-chaperone activity, being able to stimulate DnaK ATPase activity in vitro
Summary
All living organisms respond to changing external conditions by synthetizing a class of highly conserved proteins whose function is to assist protein folding and to get rid of dangerous cytoplasmic aggregates made of denatured polypeptides. The pervasive gastric pathogen Helicobacter pylori is no exception to this general rule It possesses almost all the members of the typical heat-shock proteins collection, which includes the GroEL/GroES chaperonin and the DnaK/DnaJ/GrpE chaperone system. We have shown that the protein encoded by HPG27_RS02130, the first gene of the hspR-containing operon, named CbpA, negatively affects the regulatory activity of the heat-shock repressor. This latter observation stimulates further studies to better characterize the functional relationship between HspR and CbpA, especially in the direction of defining the intersection between heat-shock genes transcriptional regulation and CbpA roles in the medically important human pathogen H. pylori
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