nhaA

Summary

Gene Symbol: nhaA
Description: sodium-proton antiporter
Alias: ECK0020, JW0018, ant, antA
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Landau M, Herz K, Padan E, Ben Tal N. Model structure of the Na+/H+ exchanger 1 (NHE1): functional and clinical implications. J Biol Chem. 2007;282:37854-63 pubmed
    ..We also suggest a hypothetical alternating-access mechanism that involves conformational changes. ..
  2. Padan E, Schuldiner S. Na+/H+ antiporters, molecular devices that couple the Na+ and H+ circulation in cells. J Bioenerg Biomembr. 1993;25:647-69 pubmed
    ..A novel signal transduction to Na+ involving nhaR, a positive regulator, controls the expression of nhaA in E. coli...
  3. Padan E, Danieli T, Keren Y, Alkoby D, Masrati G, Haliloglu T, et al. NhaA antiporter functions using 10 helices, and an additional 2 contribute to assembly/stability. Proc Natl Acad Sci U S A. 2015;112:E5575-82 pubmed publisher
    The Escherichia coli Na(+)/H(+) antiporter (Ec-NhaA) is the best-characterized of all pH-regulated Na(+)/H(+) exchangers that control cellular Na(+) and H(+) homeostasis...
  4. Gerchman Y, Rimon A, Padan E. A pH-dependent conformational change of NhaA Na(+)/H(+) antiporter of Escherichia coli involves loop VIII-IX, plays a role in the pH response of the protein, and is maintained by the pure protein in dodecyl maltoside. J Biol Chem. 1999;274:24617-24 pubmed
    Digestion with trypsin of purified His-tagged NhaA in a solution of dodecyl maltoside yields two fragments at alkaline pH but only one fragment at acidic pH...
  5. Rimon A, Tzubery T, Padan E. Monomers of the NhaA Na+/H+ antiporter of Escherichia coli are fully functional yet dimers are beneficial under extreme stress conditions at alkaline pH in the presence of Na+ or Li+. J Biol Chem. 2007;282:26810-21 pubmed
    b>NhaA, the Na(+)/H(+) antiporter of Escherichia coli, exists in the native membrane as a homodimer of which two monomers have been suggested to be attached by a beta-hairpin at the periplasmic side of the membrane...
  6. Rimon A, Tzubery T, Galili L, Padan E. Proximity of cytoplasmic and periplasmic loops in NhaA Na+/H+ antiporter of Escherichia coli as determined by site-directed thiol cross-linking. Biochemistry. 2002;41:14897-905 pubmed
    The unique trypsin cleavable site of NhaA, the Na(+)/H(+) antiporter of Escherichia coli, was exploited to detect a change in mobility of cross-linked products of NhaA by polyacrylamide gel electrophoresis...
  7. Venturi M, Seifert C, Hunte C. High level production of functional antibody Fab fragments in an oxidizing bacterial cytoplasm. J Mol Biol. 2002;315:1-8 pubmed
    ..pFAB1 we tested the cytoplasmic expression of two Fab fragments, which recognize the integral membrane protein NhaA, a bacterial Na(+)/H(+) antiporter. These antibodies differ in terms of DNA sequence and stability...
  8. Karpel R, Alon T, Glaser G, Schuldiner S, Padan E. Expression of a sodium proton antiporter (NhaA) in Escherichia coli is induced by Na+ and Li+ ions. J Biol Chem. 1991;266:21753-9 pubmed
    Regulation of expression of nhaA, the gene which encodes a Na+/H+ antiporter in Escherichia coli has been studied...
  9. Tzubery T, Rimon A, Padan E. Mutation E252C increases drastically the Km value for Na+ and causes an alkaline shift of the pH dependence of NhaA Na+/H+ antiporter of Escherichia coli. J Biol Chem. 2004;279:3265-72 pubmed
    A single Cys replacement of Glu at position 252 (E252C) in loop VIII-IX of NhaA increases drastically the Km for Na(+) (50-fold) of the Na(+)/H(+) antiporter activity of NhaA and shifts the pH dependence of NhaA activity, by one pH unit, ..
  10. Dover N, Padan E. Transcription of nhaA, the main Na(+)/H(+) antiporter of Escherichia coli, is regulated by Na(+) and growth phase. J Bacteriol. 2001;183:644-53 pubmed
    The transcription of nhaA, encoding the main Na(+)/H(+) antiporter of Escherichia coli, is induced by Na(+), regulated by NhaR, and affected by H-NS...

Detail Information

Publications92

  1. Landau M, Herz K, Padan E, Ben Tal N. Model structure of the Na+/H+ exchanger 1 (NHE1): functional and clinical implications. J Biol Chem. 2007;282:37854-63 pubmed
    ..We also suggest a hypothetical alternating-access mechanism that involves conformational changes. ..
  2. Padan E, Schuldiner S. Na+/H+ antiporters, molecular devices that couple the Na+ and H+ circulation in cells. J Bioenerg Biomembr. 1993;25:647-69 pubmed
    ..A novel signal transduction to Na+ involving nhaR, a positive regulator, controls the expression of nhaA in E. coli...
  3. Padan E, Danieli T, Keren Y, Alkoby D, Masrati G, Haliloglu T, et al. NhaA antiporter functions using 10 helices, and an additional 2 contribute to assembly/stability. Proc Natl Acad Sci U S A. 2015;112:E5575-82 pubmed publisher
    The Escherichia coli Na(+)/H(+) antiporter (Ec-NhaA) is the best-characterized of all pH-regulated Na(+)/H(+) exchangers that control cellular Na(+) and H(+) homeostasis...
  4. Gerchman Y, Rimon A, Padan E. A pH-dependent conformational change of NhaA Na(+)/H(+) antiporter of Escherichia coli involves loop VIII-IX, plays a role in the pH response of the protein, and is maintained by the pure protein in dodecyl maltoside. J Biol Chem. 1999;274:24617-24 pubmed
    Digestion with trypsin of purified His-tagged NhaA in a solution of dodecyl maltoside yields two fragments at alkaline pH but only one fragment at acidic pH...
  5. Rimon A, Tzubery T, Padan E. Monomers of the NhaA Na+/H+ antiporter of Escherichia coli are fully functional yet dimers are beneficial under extreme stress conditions at alkaline pH in the presence of Na+ or Li+. J Biol Chem. 2007;282:26810-21 pubmed
    b>NhaA, the Na(+)/H(+) antiporter of Escherichia coli, exists in the native membrane as a homodimer of which two monomers have been suggested to be attached by a beta-hairpin at the periplasmic side of the membrane...
  6. Rimon A, Tzubery T, Galili L, Padan E. Proximity of cytoplasmic and periplasmic loops in NhaA Na+/H+ antiporter of Escherichia coli as determined by site-directed thiol cross-linking. Biochemistry. 2002;41:14897-905 pubmed
    The unique trypsin cleavable site of NhaA, the Na(+)/H(+) antiporter of Escherichia coli, was exploited to detect a change in mobility of cross-linked products of NhaA by polyacrylamide gel electrophoresis...
  7. Venturi M, Seifert C, Hunte C. High level production of functional antibody Fab fragments in an oxidizing bacterial cytoplasm. J Mol Biol. 2002;315:1-8 pubmed
    ..pFAB1 we tested the cytoplasmic expression of two Fab fragments, which recognize the integral membrane protein NhaA, a bacterial Na(+)/H(+) antiporter. These antibodies differ in terms of DNA sequence and stability...
  8. Karpel R, Alon T, Glaser G, Schuldiner S, Padan E. Expression of a sodium proton antiporter (NhaA) in Escherichia coli is induced by Na+ and Li+ ions. J Biol Chem. 1991;266:21753-9 pubmed
    Regulation of expression of nhaA, the gene which encodes a Na+/H+ antiporter in Escherichia coli has been studied...
  9. Tzubery T, Rimon A, Padan E. Mutation E252C increases drastically the Km value for Na+ and causes an alkaline shift of the pH dependence of NhaA Na+/H+ antiporter of Escherichia coli. J Biol Chem. 2004;279:3265-72 pubmed
    A single Cys replacement of Glu at position 252 (E252C) in loop VIII-IX of NhaA increases drastically the Km for Na(+) (50-fold) of the Na(+)/H(+) antiporter activity of NhaA and shifts the pH dependence of NhaA activity, by one pH unit, ..
  10. Dover N, Padan E. Transcription of nhaA, the main Na(+)/H(+) antiporter of Escherichia coli, is regulated by Na(+) and growth phase. J Bacteriol. 2001;183:644-53 pubmed
    The transcription of nhaA, encoding the main Na(+)/H(+) antiporter of Escherichia coli, is induced by Na(+), regulated by NhaR, and affected by H-NS...
  11. Alhadeff R, Warshel A. Simulating the function of sodium/proton antiporters. Proc Natl Acad Sci U S A. 2015;112:12378-83 pubmed publisher
    ..This work explores the molecular origin of the function of the bacterial Na+/H+ antiporter NhaA by evaluating the energetics of the Na+ and H+ movement and then using the resulting landscape in Monte Carlo ..
  12. Kozachkov L, Padan E. Site-directed tryptophan fluorescence reveals two essential conformational changes in the Na+/H+ antiporter NhaA. Proc Natl Acad Sci U S A. 2011;108:15769-74 pubmed publisher
    b>NhaA, a Na(+)/H(+) antiporter critical for pH and Na(+) homeostasis in Escherichia coli, as well as other enterobacteria and possibly Homo sapiens, was modified for fluorescence spectroscopy by constructing a functional Trp-less NhaA ..
  13. Dover N, Higgins C, Carmel O, Rimon A, Pinner E, Padan E. Na+-induced transcription of nhaA, which encodes an Na+/H+ antiporter in Escherichia coli, is positively regulated by nhaR and affected by hns. J Bacteriol. 1996;178:6508-17 pubmed
    b>nhaA encodes an Na+/H+ antiporter in Escherichia coli which is essential for adaptation to high salinity and alkaline pH in the presence of Na+. We used Northern (RNA) analysis to measure directly the cellular levels of nhaA mRNA...
  14. Screpanti E, Padan E, Rimon A, Michel H, Hunte C. Crucial steps in the structure determination of the Na+/H+ antiporter NhaA in its native conformation. J Mol Biol. 2006;362:192-202 pubmed
    ..Recently, the first structure of this family of secondary transporters, namely of NhaA from Escherichia coli, revealed a novel fold and elucidated the molecular basis for the mechanism of transport and ..
  15. Rowbury R, Hussain N. Exposure of Escherichia coli to acid habituation conditions sensitizes it to alkaline stress. Lett Appl Microbiol. 1996;22:57-61 pubmed
    ..5 plus DNA gyrase inhibitors and was markedly reduced by himA, himD, hns, ompC and nhaA lesions. A tonB deletion mutant showed alkali sensitivity at pHo 7.0...
  16. Harel Bronstein M, Dibrov P, Olami Y, Pinner E, Schuldiner S, Padan E. MH1, a second-site revertant of an Escherichia coli mutant lacking Na+/H+ antiporters (delta nhaA delta nhaB), regains Na+ resistance and a capacity to excrete Na+ in a delta microH(+)-independent fashion. J Biol Chem. 1995;270:3816-22 pubmed
    The Escherichia coli mutant delta nhaA delta nhaB (EP432), which lacks the two specific Na+/H+ antiporter genes, is incapable of efficiently excreting Na+...
  17. Williams K, Geldmacher Kaufer U, Padan E, Schuldiner S, Kuhlbrandt W. Projection structure of NhaA, a secondary transporter from Escherichia coli, at 4.0 A resolution. EMBO J. 1999;18:3558-63 pubmed
    Electron cryomicroscopy of frozen-hydrated two-dimensional crystals of NhaA, a Na+/H+ antiporter from Escherichia coli predicted to have 12 transmembrane alpha-helices, has facilitated the calculation of a projection map of NhaA at 4...
  18. Shimamoto T, Inaba K, Thelen P, Ishikawa T, Goldberg E, Tsuda M, et al. The NhaB Na+/H+ antiporter is essential for intracellular pH regulation under alkaline conditions in Escherichia coli. J Biochem. 1994;116:285-90 pubmed
    ..coli. Introduction of nhaA gene into the mutant cells increased Na+/H+ antiporter activity, but did not restore the defective growth and ..
  19. Karpel R, Olami Y, Taglicht D, Schuldiner S, Padan E. Sequencing of the gene ant which affects the Na+/H+ antiporter activity in Escherichia coli. J Biol Chem. 1988;263:10408-14 pubmed
    ..58 kilobase pairs) which contains the ant gene. Thus, transformants of all plasmid constructs containing this segment exhibit Antup phenotype, i.e...
  20. Padan E, Gerchman Y, Rimon A, Rothman A, Dover N, Carmel Harel O. The molecular mechanism of regulation of the NhaA Na+/H+ antiporter of Escherichia coli, a key transporter in the adaptation to Na+ and H+. Novartis Found Symp. 1999;221:183-96; discussion 196-9 pubmed
    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...
  21. Calinescu O, Dwivedi M, Patiño Ruiz M, Padan E, Fendler K. Lysine 300 is essential for stability but not for electrogenic transport of the Escherichia coli NhaA Na+/H+ antiporter. J Biol Chem. 2017;292:7932-7941 pubmed publisher
    ..The NhaA antiporter of Escherichia coli is the best studied member of the Na+/H+ exchanger ..
  22. Cymer F, von Heijne G. Cotranslational folding of membrane proteins probed by arrest-peptide-mediated force measurements. Proc Natl Acad Sci U S A. 2013;110:14640-5 pubmed publisher
    ..Our findings pinpoint the earliest steps of tertiary structure formation and open up possibilities to study the cotranslational folding of polytopic membrane proteins. ..
  23. Padan E, Venturi M, Michel H, Hunte C. Production and characterization of monoclonal antibodies directed against native epitopes of NhaA, the Na+/H+ antiporter of Escherichia coli. FEBS Lett. 1998;441:53-8 pubmed
    ..In an attempt to raise monoclonal antibodies against the NhaA Na+/H+ antiporter of Escherichia coli we encountered difficulties in the screening procedure, which is based on the ..
  24. Hunte C, Screpanti E, Venturi M, Rimon A, Padan E, Michel H. Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH. Nature. 2005;435:1197-202 pubmed
    ..Their activity is tightly controlled by pH. Here we present the crystal structure of pH-downregulated NhaA, the main antiporter of Escherichia coli and many enterobacteria...
  25. Pinner E, Padan E, Schuldiner S. Kinetic properties of NhaB, a Na+/H+ antiporter from Escherichia coli. J Biol Chem. 1994;269:26274-9 pubmed
    ..The significance of the existence of two antiporters with different stoichiometries, NhaA and NhaB, active in the same cell, is discussed.
  26. Dibrov P, Rimon A, Dzioba J, Winogrodzki A, Shalitin Y, Padan E. 2-Aminoperimidine, a specific inhibitor of bacterial NhaA Na(+)/H(+) antiporters. FEBS Lett. 2005;579:373-8 pubmed
    ..Most prokaryotic antiporters, including the major NhaA family of enterobacteria, are resistant to these compounds...
  27. Kedrov A, Janovjak H, Ziegler C, Kuhlbrandt W, Muller D. Observing folding pathways and kinetics of a single sodium-proton antiporter from Escherichia coli. J Mol Biol. 2006;355:2-8 pubmed
    ..established single-molecule force spectroscopy to observe directly the stepwise folding of the Na+/H+ antiporter NhaA from Escherichia coli in vitro...
  28. Goldberg E, Arbel T, Chen J, Karpel R, Mackie G, Schuldiner S, et al. Characterization of a Na+/H+ antiporter gene of Escherichia coli. Proc Natl Acad Sci U S A. 1987;84:2615-9 pubmed
    ..A wild-type gene located within 2 kilobase pairs counterclockwise of rpsT increases the Na+/H+ antiport activity when present in multiple copies. ..
  29. Padan E, Venturi M, Gerchman Y, Dover N. Na(+)/H(+) antiporters. Biochim Biophys Acta. 2001;1505:144-57 pubmed
    ..Structure and function studies of a purified antiporter protein have as yet been conducted mainly with NhaA, the key Na(+)/H(+) antiporter of Escherichia coli...
  30. Herz K, Rimon A, Jeschke G, Padan E. Beta-sheet-dependent dimerization is essential for the stability of NhaA Na+/H+ antiporter. J Biol Chem. 2009;284:6337-47 pubmed publisher
    A structural model of the NhaA dimer showed that a beta-hairpin of each monomer combines to form a beta-sheet at the periplasmic side of the membrane...
  31. Dibrov P. Calcium transport mediated by NhaA, a Na+/H+ antiporter from Escherichia coli. FEBS Lett. 1993;336:530-4 pubmed
    In everted membrane vesicles of E. coli strain EP432/pGM42, which has only one Na+/H+ antiporter (NhaA), external CaCl2 inhibits dissipation of the respiration-dependent delta pH in response to the addition of NaCl at pH 7...
  32. Kozachkov L, Herz K, Padan E. Functional and structural interactions of the transmembrane domain X of NhaA, Na+/H+ antiporter of Escherichia coli, at physiological pH. Biochemistry. 2007;46:2419-30 pubmed
    The 3D structure of Escherichia coli NhaA, determined at pH 4, provided the first structural insights into the mechanism of antiport and pH regulation of a Na+/H+ antiporter. However, because NhaA is activated at physiological pH (pH 7...
  33. Verkhovskaya M, Barquera B, Verkhovsky M, Wikstrom M. The Na+ and K+ transport deficiency of an E. coli mutant lacking the NhaA and NhaB proteins is apparent and caused by impaired osmoregulation. FEBS Lett. 1998;439:271-4 pubmed
    Cells of the E. coli mutant EP432, which lacks the two Na+/H+ antiporters, NhaA and NhaB, have been reported to have an impaired sodium transport activity (Harel-Bronstein et al. (1995) J. Biol. Chem. 270, 3816-3822)...
  34. Dibrov P, Taglicht D. Mechanism of Na+/H+ exchange by Escherichia coli NhaA in reconstituted proteoliposomes. FEBS Lett. 1993;336:525-9 pubmed
    Purified NhaA, a Na+/H+ antiporter from Escherichia coli, reconstituted into proteoliposomes was used to study partial reactions catalyzed by this protein...
  35. Galili L, Herz K, Dym O, Padan E. Unraveling functional and structural interactions between transmembrane domains IV and XI of NhaA Na+/H+ antiporter of Escherichia coli. J Biol Chem. 2004;279:23104-13 pubmed
    A functionally important, interface domain between transmembrane segments (TMSs) IV and XI of the NhaA Na+/H+ antiporter of Escherichia coli has been unraveled...
  36. Taglicht D, Padan E, Schuldiner S. Overproduction and purification of a functional Na+/H+ antiporter coded by nhaA (ant) from Escherichia coli. J Biol Chem. 1991;266:11289-94 pubmed
    A Na+/H+ antiporter coded by the nhaA (ant) gene of Escherichia coli has been overproduced and purified...
  37. Kedrov A, Ziegler C, Muller D. Differentiating ligand and inhibitor interactions of a single antiporter. J Mol Biol. 2006;362:925-32 pubmed
    ..force spectroscopy we observe the binding of the inhibitor 2-aminoperimidine (AP) to sodium/proton antiporters NhaA from Escherichia coli...
  38. Appel M, Hizlan D, Vinothkumar K, Ziegler C, Kuhlbrandt W. Conformations of NhaA, the Na+/H+ exchanger from Escherichia coli, in the pH-activated and ion-translocating states. J Mol Biol. 2009;388:659-72 pubmed
    b>NhaA, the main sodium-proton exchanger in the inner membrane of Escherichia coli, regulates the cytosolic concentrations of H+ and Na+...
  39. Williams K. Three-dimensional structure of the ion-coupled transport protein NhaA. Nature. 2000;403:112-5 pubmed
    ..b>NhaA is a Na+/H+ antiporter of relative molecular mass 42,000, which is found in the inner membrane of Escherichia coli, ..
  40. Ohyama T, Igarashi K, Kobayashi H. Physiological role of the chaA gene in sodium and calcium circulations at a high pH in Escherichia coli. J Bacteriol. 1994;176:4311-5 pubmed
    ..The resultant mutant, TO112, deficient in both nhaA and chaA, was unable to grow at pH 8.5 in medium containing 0...
  41. Gerchman Y, Rimon A, Venturi M, Padan E. Oligomerization of NhaA, the Na+/H+ antiporter of Escherichia coli in the membrane and its functional and structural consequences. Biochemistry. 2001;40:3403-12 pubmed
    Recently, a two-dimensional crystal structure of NhaA, the Na+/H+ antiporter of Escherichia coli has been obtained [Williams, K. A., Kaufer, U. G., Padan, E., Schuldiner, S. and Kühlbrandt, W. (1999) EMBO J., 18, 3558-3563]...
  42. Sakuma T, Yamada N, Saito H, Kakegawa T, Kobayashi H. pH dependence of the function of sodium ion extrusion systems in Escherichia coli. Biochim Biophys Acta. 1998;1363:231-7 pubmed
    Escherichia coli has three systems for sodium ion extrusion, NhaA, NhaB and ChaA...
  43. Shijuku T, Saito H, Kakegawa T, Kobayashi H. Expression of sodium/proton antiporter NhaA at various pH values in Escherichia coli. Biochim Biophys Acta. 2001;1506:212-7 pubmed
    It was reported that NhaA, one of sodium/proton antiporters in Escherichia coli, was expressed at alkaline pH [J. Biol. Chem. 266 (1991) 21753]...
  44. Rowbury R. Regulatory components, including integration host factor, CysB and H-NS, that influence pH responses in Escherichia coli. Lett Appl Microbiol. 1997;24:319-28 pubmed
    ..DNA gyrase; tolerance is reduced by NaCl but not affected by Fe3+, Fe2+, glucose/cAMP or by lrp, him, fur, hns or nhaA/B lesions. Alkali tolerance (habituation), induced at pH0 8.5-9...
  45. Rahav Manor O, Carmel O, Karpel R, Taglicht D, Glaser G, Schuldiner S, et al. NhaR, a protein homologous to a family of bacterial regulatory proteins (LysR), regulates nhaA, the sodium proton antiporter gene in Escherichia coli. J Biol Chem. 1992;267:10433-8 pubmed
    ..C. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 6602-6606). In this work we show that nhaR is a regulator of nhaA, a gene encoding a Na+/H+ antiporter in Escherichia coli...
  46. Rimon A, Hunte C, Michel H, Padan E. Epitope mapping of conformational monoclonal antibodies specific to NhaA Na+/H+ antiporter: structural and functional implications. J Mol Biol. 2008;379:471-81 pubmed publisher
    The recently determined crystal structure of NhaA, the Na(+)/H(+) antiporter of Escherichia coli, showed that the previously constructed series of NhaA-alkaline phosphatase (PhoA) fusions correctly predicted the topology of NhaA's 12 ..
  47. Inaba K, Kuroda T, Shimamoto T, Kayahara T, Tsuda M, Tsuchiya T. Lithium toxicity and Na+(Li+)/H+ antiporter in Escherichia coli. Biol Pharm Bull. 1994;17:395-8 pubmed
    ..Two Na+(Li+)/H+ antiporters (NhaA system and NhaB system) are known to be present in E. coli...
  48. Lee C, Yashiro S, Dotson D, Uzdavinys P, Iwata S, Sansom M, et al. Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights. J Gen Physiol. 2014;144:529-44 pubmed publisher
    ..Here, we report a crystal form of the prototypical sodium-proton antiporter NhaA from Escherichia coli in which the protein is seen as a dimer...
  49. Wiebe C, Dibattista E, Fliegel L. Functional role of polar amino acid residues in Na+/H+ exchangers. Biochem J. 2001;357:1-10 pubmed
    ..Histidine residues have been shown to be important in the function of the E. coli Na(+)/H(+) exchanger NhaA and in the yeast Na(+)/H(+) exchanger sod2. In E...
  50. Venturi M, Hunte C. Monoclonal antibodies for the structural analysis of the Na+/H+ antiporter NhaA from Escherichia coli. Biochim Biophys Acta. 2003;1610:46-50 pubmed
    ..In this review, we focus on the methods used to generate monoclonal antibodies against the NhaA antiporter from Escherichia coli as a paradigm of secondary transporters...
  51. Pinner E, Kotler Y, Padan E, Schuldiner S. Physiological role of nhaB, a specific Na+/H+ antiporter in Escherichia coli. J Biol Chem. 1993;268:1729-34 pubmed
    ..267, 11064-11068). In order to elucidate the role of nhaB in Na+ and H+ ions physiology and its interaction with nhaA, we generated mutants in which the chromosomal gene has been inactivated by insertion/deletion...
  52. Taglicht D, Padan E, Schuldiner S. Proton-sodium stoichiometry of NhaA, an electrogenic antiporter from Escherichia coli. J Biol Chem. 1993;268:5382-7 pubmed
    The H+:Na+ exchange stoichiometry of NhaA, a sodium-proton antiporter coded by the nhaA gene of Escherichia coli, has been determined using purified NhaA protein reconstituted into sodium-loaded proteoliposomes...
  53. Maes M, Rimon A, Kozachkov Magrisso L, Friedler A, Padan E. Revealing the ligand binding site of NhaA Na+/H+ antiporter and its pH dependence. J Biol Chem. 2012;287:38150-7 pubmed publisher
    ..In most cases, their activity is tightly pH-regulated. NhaA, the main antiporter of Escherichia coli, has homologues in all biological kingdoms...
  54. Herz K, Rimon A, Olkhova E, Kozachkov L, Padan E. Transmembrane segment II of NhaA Na+/H+ antiporter lines the cation passage, and Asp65 is critical for pH activation of the antiporter. J Biol Chem. 2010;285:2211-20 pubmed publisher
    The crystal structure of Escherichia coli NhaA determined at pH 4 has provided insights into the mechanism of activity of a pH-regulated Na+/H+ antiporter. However, because NhaA is activated at physiological pH (pH 5.5-8...
  55. Zuber D, Krause R, Venturi M, Padan E, Bamberg E, Fendler K. Kinetics of charge translocation in the passive downhill uptake mode of the Na+/H+ antiporter NhaA of Escherichia coli. Biochim Biophys Acta. 2005;1709:240-50 pubmed
    The Na+/H+ antiporter NhaA is the main Na+ extrusion system in E. coli...
  56. Thelen P, Tsuchiya T, Goldberg E. Characterization and mapping of a major Na+/H+ antiporter gene of Escherichia coli. J Bacteriol. 1991;173:6553-7 pubmed
    ..An isogenic nhaA (formerly antA) deletion strain, however, is not significantly different from wild type in this respect...
  57. Inoue H, Noumi T, Shimomura T, Takimoto N, Tsuchiya T, Kanazawa H. pH-dependent growth retardation of Escherichia coli caused by overproduction of Na+/H+ antiporter. Biol Pharm Bull. 1998;21:1128-33 pubmed
    The overproduction of Na+/H+ antiporter NhaA in Escherichia coli caused growth retardation. Quantities and the activity of the antiporter were studied for their causative roles in terms of this retardation...
  58. Padan E, Kozachkov L, Herz K, Rimon A. NhaA crystal structure: functional-structural insights. J Exp Biol. 2009;212:1593-603 pubmed publisher
    ..Many Na(+)/H(+) antiporters are tightly regulated by pH. Escherichia coli NhaA Na(+)/H(+) antiporter, a prototype pH-regulated antiporter, exchanges 2 H(+) for 1 Na(+) (or Li(+))...
  59. Olkhova E, Kozachkov L, Padan E, Michel H. Combined computational and biochemical study reveals the importance of electrostatic interactions between the "pH sensor" and the cation binding site of the sodium/proton antiporter NhaA of Escherichia coli. Proteins. 2009;76:548-59 pubmed publisher
    ..The crystal structure of NhaA has provided a basis to explore the mechanism of ion exchange and its unique regulation by pH...
  60. Tzubery T, Rimon A, Padan E. Structure-based functional study reveals multiple roles of transmembrane segment IX and loop VIII-IX in NhaA Na+/H+ antiporter of Escherichia coli at physiological pH. J Biol Chem. 2008;283:15975-87 pubmed publisher
    The three-dimensional crystal structure of Escherichia coli NhaA determined at pH 4 provided the first structural insights into the mechanism of antiport and pH regulation of a Na(+)/H(+) antiporter...
  61. Otzen D, Sehgal P, Nesgaard L. Alternative membrane protein conformations in alcohols. Biochemistry. 2007;46:4348-59 pubmed
    ..protein stability and solubility, using the two detergent-solubilized alpha-helical membrane proteins DsbB and NhaA. Both proteins precipitate extensively at intermediate concentrations of alcohols, forming states with extensive (..
  62. Padan E. The enlightening encounter between structure and function in the NhaA Na+-H+ antiporter. Trends Biochem Sci. 2008;33:435-43 pubmed publisher
    ..Many Na(+)-H(+) antiporters are tightly regulated by pH. Escherichia coli NhaA, a prototype pH-regulated antiporter, exchanges 2H(+) for 1Na(+) (or Li(+))...
  63. Olami Y, Rimon A, Gerchman Y, Rothman A, Padan E. Histidine 225, a residue of the NhaA-Na+/H+ antiporter of Escherichia coli is exposed and faces the cell exterior. J Biol Chem. 1997;272:1761-8 pubmed
    Cysteine residues were found nonessential in the mechanism of the NhaA antiporter activity of Escherichia coli...
  64. Verkhovskaya M, Verkhovsky M, Wikstrom M. The respiration-driven active sodium transport system in E. coli does not function with lithium. FEBS Lett. 1996;388:217-8 pubmed
    ..coli [Verkhovskaya, M.L., Verkhovsky, M.I. and Wikstrom, M. (1996) Biochim. Biophys. Acta 1273, 207-216]. In contrast to the Na+/H+ antiporters, the AST system is inhibited by Li+. ..
  65. Džafić E, Klein O, Screpanti E, Hunte C, Mäntele W. Flexibility and dynamics of NhaA Na+/H+-antiporter of Escherichia coli studied by Fourier transform infrared spectroscopy. Spectrochim Acta A Mol Biomol Spectrosc. 2009;72:102-9 pubmed publisher
    b>NhaA (41,355Da) is a Na(+)/H(+) antiporter of Escherichia coli which plays a central role in regulation of intracellular pH, cellular Na(+) content, and cell volume [E. Padan, S. Schuldiner, J. Exp. Biol. 196 (1994) 443]...
  66. Beth A. How to assemble the parts: structures of protein complexes from their components. Biophys J. 2007;93:3339 pubmed
  67. Serrano R. Salt tolerance in plants and microorganisms: toxicity targets and defense responses. Int Rev Cytol. 1996;165:1-52 pubmed
    ..In Escherichia coli, the Na(+)-H+ antiporter encoded by the nhaA gene is essential for salt tolerance...
  68. Noumi T, Inoue H, Sakurai T, Tsuchiya T, Kanazawa H. Identification and characterization of functional residues in a Na+/H+ antiporter (NhaA) from Escherichia coli by random mutagenesis. J Biochem. 1997;121:661-70 pubmed
    Forty-one mutants were isolated by means of random PCR mutagenesis of the Escherichia coli Na+/H+ antiporter (nhaA), which could not support the growth of a nhaAnhaB mutant (HIT delta AB-) on plates containing 0.15 M LiCl (pH 7.5) or 0...
  69. Xiang M, Feng M, Muend S, Rao R. A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension. Proc Natl Acad Sci U S A. 2007;104:18677-81 pubmed
    ..The NHA (sodium hydrogen antiporter) family members share significant sequence similarity with Escherichia coli NhaA, including a conserved double aspartate motif in predicted transmembrane 5...
  70. Ohyama T, Imaizumi R, Igarashi K, Kobayashi H. Escherichia coli is able to grow with negligible sodium ion extrusion activity at alkaline pH. J Bacteriol. 1992;174:7743-9 pubmed
    The Escherichia coli mutant NM81, which is deficient in the nhaA gene for the sodium/proton antiporter, still has a sodium ion extrusion activity because of a second antiporter encoded by nhaB (E. Padan, N. Maisler, D. Taglicht, R...
  71. Padan E, Bibi E, Ito M, Krulwich T. Alkaline pH homeostasis in bacteria: new insights. Biochim Biophys Acta. 2005;1717:67-88 pubmed
    ..New insights into the pH-dependent Na(+)/H(+) antiporter NhaA that plays an important role in Escherichia coli have recently emerged from the determination of the structure of ..
  72. Kedrov A, Appel M, Baumann H, Ziegler C, Muller D. Examining the dynamic energy landscape of an antiporter upon inhibitor binding. J Mol Biol. 2008;375:1258-66 pubmed
    ..single-molecule force spectroscopy to detect and locate interactions within the functional Na(+)/H(+) antiporter NhaA from Escherichia coli...
  73. Galili L, Rothman A, Kozachkov L, Rimon A, Padan E. Trans membrane domain IV is involved in ion transport activity and pH regulation of the NhaA-Na(+)/H(+) antiporter of Escherichia coli. Biochemistry. 2002;41:609-17 pubmed
    We have previously shown that the activity of NhaA is regulated by pH and found mutations that affect dramatically the pH dependence of the rate but not the K(m) (for Na(+) and Li(+)) of NhaA...
  74. Rimon A, Gerchman Y, Olami Y, Schuldiner S, Padan E. Replacements of histidine 226 of NhaA-Na+/H+ antiporter of Escherichia coli. Cysteine (H226C) or serine (H226S) retain both normal activity and pH sensitivity, aspartate (H226D) shifts the pH profile toward basic pH, and alanine (H226A) inactivates t. J Biol Chem. 1995;270:26813-7 pubmed
    We have previously shown that replacement of His-226 in the NhaA Na+/H+ antiporter of Escherichia coli to Arg (H226R) shifts the pH profile of the antiporter toward acidic pH and as a result of delta nhaA delta nhaB strain bearing this ..
  75. Gupta K, Donlan J, Hopper J, Uzdavinys P, Landreh M, Struwe W, et al. The role of interfacial lipids in stabilizing membrane protein oligomers. Nature. 2017;541:421-424 pubmed publisher
    ..We hypothesized that lipids are essential for dimerization of the Na+/H+ antiporter NhaA from E...
  76. Ravna A, Sylte I, Dahl S. Molecular model of the Escherichia coli Na1/H1 antiporter NhaA. Receptors Channels. 2001;7:319-28 pubmed
    ..electron density projection map of the ion-coupled membrane protein Escherichia coli Na+/H+ antiporter (NhaA) was recently published...
  77. Carmel O, Rahav Manor O, Dover N, Shaanan B, Padan E. The Na+-specific interaction between the LysR-type regulator, NhaR, and the nhaA gene encoding the Na+/H+ antiporter of Escherichia coli. EMBO J. 1997;16:5922-9 pubmed
    ..purified NhaR and a highly purified His-tagged NhaR derivative to identify the cis-regulatory sequences of nhaA recognized by NhaR and to study the specific effect of Na+ on this interaction...
  78. Rimon A, Gerchman Y, Kariv Z, Padan E. A point mutation (G338S) and its suppressor mutations affect both the pH response of the NhaA-Na+/H+ antiporter as well as the growth phenotype of Escherichia coli. J Biol Chem. 1998;273:26470-6 pubmed
    pH controls the activity of the NhaA Na+/H+ antiporter of Escherichia coli. In the present work we show that replacement of glycine 338 of NhaA with serine (G338S) alleviates the pH control of the antiporter...
  79. Inoue H, Noumi T, Tsuchiya T, Kanazawa H. Essential aspartic acid residues, Asp-133, Asp-163 and Asp-164, in the transmembrane helices of a Na+/H+ antiporter (NhaA) from Escherichia coli. FEBS Lett. 1995;363:264-8 pubmed
    ..Four Asp residues were located in the putative transmembrane helices of the Escherichia coli Na+/H+ antiporter, NhaA. We replaced each of these Asp residues by Asn in plasmid encoded nhaA and expressed these constructs in an E...
  80. Gerchman Y, Olami Y, Rimon A, Taglicht D, Schuldiner S, Padan E. Histidine-226 is part of the pH sensor of NhaA, a Na+/H+ antiporter in Escherichia coli. Proc Natl Acad Sci U S A. 1993;90:1212-6 pubmed
    The nhaA gene of Escherichia coli, which encodes a pH-activated Na+/H+ antiporter, has been modified; six of its eight histidine codons were mutated to arginine codons by site-directed mutagenesis, yielding the mutations H254R-H257R (a ..
  81. Kedrov A, Muller D. Characterizing folding, structure, molecular interactions and ligand gated activation of single sodium/proton antiporters. Naunyn Schmiedebergs Arch Pharmacol. 2006;372:400-12 pubmed
    Using the example of sodium/proton antiporter from Escherichia coli NhaA, we review the capabilities of single-molecule atomic force microscopy and force spectroscopy to observe structural and functional insights of a membrane protein, ..
  82. Olkhova E, Padan E, Michel H. The influence of protonation states on the dynamics of the NhaA antiporter from Escherichia coli. Biophys J. 2007;92:3784-91 pubmed
    The crystal structure of NhaA Na(+)/H(+) antiporter of Escherichia coli has provided a basis to explore the mechanism of Na(+) and H(+) exchange and its regulation by pH...
  83. Verkhovskaya M, Verkhovsky M, Wikstrom M. K+-dependent Na+ transport driven by respiration in Escherichia coli cells and membrane vesicles. Biochim Biophys Acta. 1996;1273:207-16 pubmed
    ..coli mutant from which the genes encoding the two known electrogenic Na+/nH+ antiporters nhaA and nhaB were deleted transported Na+ as well as did vesicles from wild-type cells...
  84. Olkhova E, Hunte C, Screpanti E, Padan E, Michel H. Multiconformation continuum electrostatics analysis of the NhaA Na+/H+ antiporter of Escherichia coli with functional implications. Proc Natl Acad Sci U S A. 2006;103:2629-34 pubmed
    ..continuum electrostatics method to investigate the protonation states of residues in the sodium proton exchanger NhaA from Escherichia coli, the structure of which has been determined recently by x-ray crystallography...
  85. Padan E, Schuldiner S. Molecular physiology of the Na+/H+ antiporter in Escherichia coli. J Exp Biol. 1994;196:443-56 pubmed
    ..In Escherichia coli, two Na+/H+ antiporter genes, nhaA and nhaB, have been cloned...
  86. Padan E, Maisler N, Taglicht D, Karpel R, Schuldiner S. Deletion of ant in Escherichia coli reveals its function in adaptation to high salinity and an alternative Na+/H+ antiporter system(s). J Biol Chem. 1989;264:20297-302 pubmed
    We have deleted the chromosomal ant gene from Escherichia coli by substitution with the kan gene, which encodes kanamycin resistance. The delta ant strains obtained cannot adapt to high sodium concentrations (700 mM, pH 6...
  87. Appel M, Hizlan D, Vinothkumar K, Ziegler C, Kuhlbrandt W. Conformations of NhaA, the Na/H exchanger from Escherichia coli, in the pH-activated and ion-translocating states. J Mol Biol. 2009;386:351-65 pubmed publisher
    b>NhaA, the main sodium-proton exchanger in the inner membrane of Escherichia coli, regulates the cytosolic concentrations of H and Na. It is inactive at acidic pH, becomes active between pH 6 and pH 7, and reaches maximum activity at pH 8...
  88. Carmel O, Dover N, Rahav Manor O, Dibrov P, Kirsch D, Karpel R, et al. A single amino acid substitution (Glu134-->Ala) in NhaR1 increases the inducibility by Na+ of the product of nhaA, a Na+/H+ antiporter gene in Escherichia coli. EMBO J. 1994;13:1981-9 pubmed
    ..This was demonstrated by sequence analysis showing that the mutant contains a wild-type nhaA but nhaR1 instead of nhaR and by the finding that nhaR1 cloned in a plasmid confers the NhaAup phenotype...
  89. Hilger D, Jung H, Padan E, Wegener C, Vogel K, Steinhoff H, et al. Assessing oligomerization of membrane proteins by four-pulse DEER: pH-dependent dimerization of NhaA Na+/H+ antiporter of E. coli. Biophys J. 2005;89:1328-38 pubmed
    The pH dependence of the structure of the main Na(+)/H(+) antiporter NhaA of Escherichia coli is studied by continuous-wave (CW) and pulse electron paramagnetic resonance (EPR) techniques on singly spin-labeled mutants...