The molecular mechanism of regulation of the NhaA Na+/H+ antiporter of Escherichia coli, a key transporter in the adaptation to Na+ and H+.
The NhaA Na+/H+ antiporter is the main system responsible for adaptation to Na+ and alkaline pH (in the presence of Na+) in Escherichia coli and many other enteric bacteria. It is under intricate control. At the protein level it is regulated directly by pH, one of its regulatory signals. A pH shift from 7 to 8.5 activates the antiporter and, in a fashion correlated with the activity change, confers a conformation change that, in isolated membrane vesicles, is reflected in the exposure of trypsin-cleavable sites. H225 and G338 are essential for the pH response of NhaA. nhaA transcription is dependent on NhaR, a positive regulator of the LysR family, and is regulated by Na+, the other environmental signal. Na+ affects the NhaR/nhaA interaction directly by changing the footprint of NhaR on nhaA in a pH-dependent fashion. The expression of nhaA is also under global regulation of H-NS. We suggest that the pattern of regulation of nhaA found in E. coli is a paradigm for the response of proteins and genes to H+ and Na+, the most common ions that challenge every cell.
Padan
E
E
Hebrew University of Jerusalem, Department of Microbial and Molecular Ecology, Jerusalem, Israel.
Gerchman
Y
Y
Rimon
A
A
Rothman
A
A
Dover
N
N
Carmel-Harel
O
O
D000222:Adaptation, Physiological / Q000502:physiology*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000378:metabolism / Q000502:physiology*; D029968:Escherichia coli Proteins; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011522:Protons; D012964:Sodium; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; C102839:NhaA protein, E coli; C491047:NhaB protein, E coli; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; D014157:Transcription Factors; C074687:nhaR protein, E coli; D012964:Sodium