Conserved amphiphilic feature is essential for periplasmic chaperone HdeA to support acid resistance in enteric bacteria.
The extremely acidic environment of the mammalian stomach (pH 1-3) represents a stressful challenge for enteric pathogenic bacteria, including Escherichia coli, Shigella and Brucella. The hdeA (hns-dependent expression A) gene was found to be crucial for the survival of these enteric bacteria under extremely low pH conditions. We recently demonstrated that HdeA is able to exhibit chaperone-like activity exclusively within the stomach pH range by transforming from a well-folded conformation at higher pH values (above pH 3) into an unfolded conformation at extremely low pH values (below pH 3). This study was performed to characterize the action mechanisms and underlying specific structural features for HdeA to function in this unfolded conformation. In the present study, we demonstrate that the conserved 'amphiphilic' feature of HdeA, i.e. the exposure of the conserved hydrophobic region and highly charged terminal regions, is essential for exhibiting chaperone-like activity under extremely low pH conditions. Mutations that disrupt this amphiphilic feature markedly reduced the chaperone-like activity of HdeA. The results also strongly suggest that this acid-induced chaperone-like activity of HdeA is crucial for acid resistance of the enteric bacteria. Moreover, our new understanding of this amphiphilic structural feature of HdeA helps to better interpret how this unfolded (disordered) conformation could be functionally active.
Wu
Ye E
YE
National Laboratory of Protein Engineering and Plant Genetic Engineering, School of Life Sciences, Peking University, Beijing 100871, China.
Hong
Weizhe
W
Liu
Chong
C
Zhang
Lingqing
L
Chang
Zengyi
Z
D000595:Amino Acid Sequence; D000818:Animals; D002002:Brucella / Q000472:pathogenicity / Q000502:physiology*; D004926:Escherichia coli / Q000472:pathogenicity / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D033902:Periplasmic Binding Proteins / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D016415:Sequence Alignment; D012760:Shigella / Q000472:pathogenicity / Q000502:physiology*; D014633:Valine / Q000378:metabolism
D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D033902:Periplasmic Binding Proteins; C028003:RbsB protein, E coli; C084501:hdeA protein, E coli; D014633:Valine