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The Mrp system: a giant among monovalent cation/proton antiporters?

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Abstract

Mrp systems are a novel and broadly distributed type of monovalent cation/proton antiporter of bacteria and archaea. Monovalent cation/proton antiporters are membrane transport proteins that catalyze efflux of cytoplasmic sodium, potassium or lithium ions in exchange for external hydrogen ions (protons). Other known monovalent cation antiporters are single gene products, whereas Mrp systems have been proposed to function as hetero-oligomers. A mrp operon typically has six or seven genes encoding hydrophobic proteins all of which are required for optimal Mrp-dependent sodium-resistance. There is little sequence similarity of Mrp proteins to other antiporters but three of these proteins have significant sequence similarity to membrane embedded subunits of ion-translocating electron transport complexes. Mrp antiporters have essential roles in the physiology of alkaliphilic and neutralophilic Bacillus species, nitrogen-fixing Sinorhizobium meliloti and in the pathogen Staphylococcus aureus, although these bacteria contain multiple monovalent cation/proton antiporters. The wide distribution of Mrp systems leads to the anticipation of important roles in an even wider variety of pathogens, extremophiles and environmentally important organisms. Here, the distribution, established physiological roles and catalytic activities of Mrp systems are reviewed, hypotheses regarding their complexity are discussed and major open questions about their function are highlighted.

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Abbreviations

Δp:

Transmembrane electrical potential of protons, negative and alkaline in

ΔpH:

Transmembrane pH gradient

ΔΨ:

Transmembrane electrical potential, negative in

IPTG:

Iso-propyl-β-D-thiogalactopyranoside

ND and Nuo:

Protein subunit designations for, respectively, eukaryotic and bacterial Ndh-1, i.e. proton-pumping NADH quinone oxidoreductase (Complex I)

Ndh-2:

NADH quinone oxidoreductase that is not coupled to cation efflux

References

  • Andrews SC et al. (1997) A 12-cistron Escherichia coli operon (hyf) encoding a putative proton-translocating formate hydrogenlyase system. Microbiology 143(Pt 11):3633–3647

    CAS  PubMed  Google Scholar 

  • Baumer S, Ide T, Jacobi C, Johann A, Gottschalk G, Deppenmeier U (2000) The F420H2 dehydrogenase from Methanosarcina mazei is a Redox-driven proton pump closely related to NADH dehydrogenases. J Biol Chem 275:17968–17973

    Article  CAS  PubMed  Google Scholar 

  • Booth IR (1985) Regulation of cytoplasmic pH in bacteria. Microbiol Rev 49:359–378

    CAS  PubMed  Google Scholar 

  • Bravo A (1997) Phylogenetic relationships of Bacillus thuringiensis delta-endotoxin family proteins and their functional domains. J Bacteriol 179:2793–2801

    CAS  PubMed  Google Scholar 

  • Buurman ET, Teixeira de Mattos MJ, Neijssel OM (1991) Futile cycling of ammonium ions via the high affinity potassium uptake system (Kdp) of Escherichia coli. Arch Microbiol 155:391–395

    Article  CAS  PubMed  Google Scholar 

  • Cheng J, Guffanti AA, Wang W, Krulwich TA, Bechhofer DH (1996) Chromosomal tetA(L) gene of Bacillus subtilis: regulation of expression and physiology of a tetA(L) deletion strain. J Bacteriol 178:2853–2860

    CAS  PubMed  Google Scholar 

  • Dzioba J, Ostroumov E, Winogrodzki A, Dibrov P (2002) Cloning, functional expression in Escherichia coli and primary characterization of a new Na+/H+ antiporter, NhaD, of Vibrio cholerae. Mol Cell Biochem 229:119–124

    Article  CAS  PubMed  Google Scholar 

  • Fox JD, Kerby RL, Roberts GP, Ludden PW (1996) Characterization of the CO-induced, CO-tolerant hydrogenase from Rhodospirillum rubrum and the gene encoding the large subunit of the enzyme. J Bacteriol 178:1515–1524

    CAS  PubMed  Google Scholar 

  • Friedrich T (2001) Complex I: a chimaera of a redox and conformation-driven proton pump? J Bioenerg Biomembr 33:169–177

    Article  CAS  PubMed  Google Scholar 

  • Friedrich T, Scheide D (2000) The respiratory complex I of bacteria, archaea and eukarya and its module common with membrane-bound multisubunit hydrogenases. FEBS Lett 479:1–5

    Article  CAS  PubMed  Google Scholar 

  • Friedrich T, Weiss H (1997) Modular evolution of the respiratory NADH:ubiquinone oxidoreductase and the origin of its modules. J Theor Biol 187:529–540

    Article  Google Scholar 

  • Gerchman Y, Rimon A, Venturi M, Padan E (2001) Oligomerization of NhaA, the Na+/H+ antiporter of Escherichia coli in the membrane and its functional and structural consequences. Biochemistry 40:3403–3412

    Article  CAS  PubMed  Google Scholar 

  • Hamamoto T et al. (1994) Characterization of a gene responsible for the Na+/H+ antiporter system of alkalophilic Bacillus species strain C-125. Mol Microbiol 14:939–946

    CAS  PubMed  Google Scholar 

  • Hase CC, Barquera B (2001) Role of sodium bioenergetics in Vibrio cholerae. Biochim Biophys Acta 1505:169–178

    CAS  PubMed  Google Scholar 

  • Henikoff JG, Henikoff S (1996) Blocks database and its applications. Methods Enzymol 266:88–105

    CAS  PubMed  Google Scholar 

  • Henikoff JG, Pietrokovski S, Henikoff S (1997) Recent enhancements to the Blocks Database servers. Nucleic Acids Res 25:222–225

    Article  CAS  PubMed  Google Scholar 

  • Herz K, Vimont S, Padan E, Berche P (2003) Roles of NhaA, NhaB, and NhaD Na+/H+ antiporters in survival of Vibrio cholerae in a saline environment. J Bacteriol 185:1236–1244

    Article  CAS  PubMed  Google Scholar 

  • Hiramatsu T, Kodama K, Kuroda T, Mizushima T, Tsuchiya T (1998) A putative multisubunit Na+/H+ antiporter from Staphylococcus aureus. J Bacteriol 180:6642–6648

    CAS  PubMed  Google Scholar 

  • Hung DT, Mekalanos JJ (2005) Bile acids induce cholera toxin expression in Vibrio cholerae in a ToxT-independent manner. Proc Natl Acad Sci USA 102:8028–8033

    Google Scholar 

  • Ito M et al (2004) MotPS is the stator-force generator for motility of alkaliphilic Bacillus, and its homologue is a second functional Mot in Bacillus subtilis. Mol Microbiol 53:1035–1049

    Article  CAS  PubMed  Google Scholar 

  • Ito M, Guffanti AA, Oudega B, Krulwich TA (1999) mrp, a multigene, multifunctional locus in Bacillus subtilis with roles in resistance to cholate and to Na+ and in pH homeostasis. J Bacteriol 181:2394–2402

    CAS  PubMed  Google Scholar 

  • Ito M, Guffanti AA, Wang W, Krulwich TA (2000) Effects of nonpolar mutations in each of the seven Bacillus subtilis mrp genes suggest complex interactions among the gene products in support of Na+ and alkali but not cholate resistance. J Bacteriol 182:5663–5670

    Article  CAS  PubMed  Google Scholar 

  • Ito M, Guffanti AA, Krulwich TA (2001) Mrp-dependent Na+/H+ antiporters of Bacillus exhibit characteristics that are unanticipated for completely secondary active transporters. FEBS Lett 496:117–120

    Article  CAS  PubMed  Google Scholar 

  • Ji Y et al. (2001) Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA. Science 293:2266–2269

    Article  CAS  PubMed  Google Scholar 

  • Kitada M, Kosono S, Kudo T (2000) The Na+/H+ antiporter of alkaliphilic Bacillus sp. Extremophiles 4:253–258

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi K et al (2003) Essential Bacillus subtilis genes. Proc Natl Acad Sci USA 100:4678–4683

    Article  CAS  PubMed  Google Scholar 

  • Kosono S, Morotomi S, Kitada M, Kudo T (1999) Analyses of a Bacillus subtilis homologue of the Na+/H+ antiporter gene which is important for pH homeostasis of alkaliphilic Bacillus sp. C-125. Biochim Biophys Acta 1409:171–175

    CAS  PubMed  Google Scholar 

  • Kosono S, Ohashi Y, Kawamura F, Kitada M, Kudo T (2000) Function of a principal Na+/H+ antiporter, ShaA, is required for initiation of sporulation in Bacillus subtilis. J Bacteriol 182:898–904

    Article  CAS  PubMed  Google Scholar 

  • Kosono S, Asai K, Sadaie Y, Kudo T (2004) Altered gene expression in the transition phase by disruption of a Na+/H+ antiporter gene (shaA) in Bacillus subtilis. FEMS Microbiol Lett 232:93–99

    Article  CAS  PubMed  Google Scholar 

  • Krulwich TA (1995) Alkaliphiles: ‘basic’ molecular problems of pH tolerance and bioenergetics. Mol Microbiol 15:403–410

    CAS  PubMed  Google Scholar 

  • Krulwich TA, Ito M, Gilmour R, Hicks DB, Guffanti AA (1998) Energetics of alkaliphilic Bacillus species: physiology and molecules. Adv Microb Physiol 40:401–438

    CAS  PubMed  Google Scholar 

  • Krulwich TA, Guffanti AA, Ito M (1999) pH tolerance in Bacillus: alkaliphile vs. non-alkaliphile. In: Mechanisms by which bacterial cells respond to pH. Novartis Found Symp 221, Wiley, Chichester, pp 167–182

  • Krulwich TA, Ito M, Guffanti AA (2001) The Na+-dependence of alkaliphily in Bacillus. Biochim Biophys Acta 1505:158–168

    CAS  PubMed  Google Scholar 

  • Kudo T, Hino M, Kitada M, Horikoshi K (1990) DNA sequences required for the alkalophily of Bacillus sp. strain C-125 are located close together on its chromosomal DNA. J Bacteriol 172:7282–7283

    CAS  PubMed  Google Scholar 

  • Künkel A, Vorholt JA, Thauer RK, Hedderich R (1998) An Escherichia coli hydrogenase-3-type hydrogenase in methanogenic archaea. Eur J Biochem 252:467–476

    Article  PubMed  Google Scholar 

  • Leonard K, Haiker H, Weiss H (1987) Three-dimensional structure of NADH: ubiquinone reductase (complex I) from Neurospora mitochondria determined by electron microscopy of membrane crystals. J Mol Biol 194:277–286

    Article  CAS  PubMed  Google Scholar 

  • Lewinson O, Padan E, Bibi E (2004) Alkalitolerance: a biological function for a multidrug transporter in pH homeostasis. Proc Natl Acad Sci USA 101:14073–14078

    Article  CAS  PubMed  Google Scholar 

  • Li X, Alvarez B, Casey JR, Reithmeier RA, Fliegel L (2002) Carbonic anhydrase II binds to and enhances activity of the Na+/H+ exchanger. J Biol Chem 277:36085–36091

    Article  CAS  PubMed  Google Scholar 

  • MacNab RM, Castle AM (1987) A variable stoichiometry model for pH homeostasis in bacteria. Biophys J 52:637–647

    CAS  PubMed  Google Scholar 

  • Mathiesen C, Hägerhäll C (2002) Transmembrane topology of the NuoL, M and N subunits of NADH:quinone oxidoreductase and their homologues among membrane-bound hydrogenases and bona fide antiporters. Biochim Biophys Acta 1556:121–132

    CAS  PubMed  Google Scholar 

  • Mathiesen C, Hägerhäll C (2003) The ‘antiporter module’ of respiratory chain Complex I includes the MrpC/NuoK subunit – a revision of the modular evolution scheme. FEBS Lett 5459:7–13

    Article  Google Scholar 

  • Orlowski J, Grinstein S (2004) Diversity of the mammalian sodium/proton exchanger SLC9 gene family Eur. J Physiol 447:549–565

    Article  CAS  Google Scholar 

  • Padan E, Krulwich TA (2000) Sodium stress. In: Storz G, Hengge-Aronis R (eds) ASM Press, Washington, DC, pp117–130

  • Padan E, Schuldiner S (1996) Bacterial Na+/H+ antiporters – molecular biology, biochemistry and physiology. In: Konings WN, Kaback HR, Lolkema J (eds) The Handbook of Biological Physics, vol II. Transport processes in membranes. Elsevier Science, Amsterdam, pp 501–531

  • Padan E, Venturi M, Gerchman Y, Dover N (2001) Na+/H+ antiporters. Biochim Biophys Acta 1505:144–157

    CAS  PubMed  Google Scholar 

  • Padan E, Tzubery T, Herz K, Kozachkov L, Rimon A, Galili L (2004) NhaA of Escherichia coli, as a model of a pH-regulated Na+/H+ antiporter. Biochim Biophys Acta 1658:2–13

    CAS  PubMed  Google Scholar 

  • Putnoky P et al (1998) The pha gene cluster of Rhizobium meliloti involved in pH adaptation and symbiosis encodes a novel type of K+ efflux system. Mol Microbiol 28:1091–1101

    Google Scholar 

  • Safferling M et al (2003) TetL tetracycline efflux protein from Bacillus subtilis is a dimer in the membrane and in detergent solution. Biochemistry 42:13969–13976

    Article  CAS  PubMed  Google Scholar 

  • Saier MH Jr et al (1999) Phylogenetic characterization of novel transport protein families revealed by genome analyses. Biochim Biophys Acta 1422:1–56

    Google Scholar 

  • Sapra R, Verhagen MF, Adams MW (2000) Purification and characterization of a membrane-bound hydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus. J Bacteriol 182:3423–3428

    Article  CAS  PubMed  Google Scholar 

  • Sapra R, Bagramyan K, Adams MW (2003) A simple energy-conserving system: proton reduction coupled to proton translocation. Proc Natl Acad Sci USA 100:7545–7550

    Article  CAS  PubMed  Google Scholar 

  • Sauter M, Bohm R, Bock A (1992) Mutational analysis of the operon (hyc) determining hydrogenase 3 formation in Escherichia coli. Mol Microbiol 6:1523–1532

    CAS  PubMed  Google Scholar 

  • Sazanov LA, Peak-Chew SY, Fearnley IM, Walker JE (2000) Resolution of the membrane domain of bovine complex I into subcomplexes: implications for the structural organization of the enzyme. Biochemistry 39:7229–7235

    Article  CAS  PubMed  Google Scholar 

  • Seto Y, Hashimoto M, Usami R, Hamamoto T, Kudo T, Horikoshi K (1995) Characterization of a mutation responsible for an alkali-sensitive mutant, 18224, of alkaliphilic Bacillus sp. strain C-125. Biosci Biotechnol Biochem 59:1364–1366

    CAS  PubMed  Google Scholar 

  • Shijuku T, Saito H, Kakegawa T, Kobayashi H (2001) Expression of sodium/proton antiporter NhaA at various pH values in Escherichia coli. Biochim Biophys Acta 1506:212–217

    CAS  PubMed  Google Scholar 

  • Silva PJ et al. (2000) Enzymes of hydrogen metabolism in Pyrococcus furiosus. Eur J Biochem 267:6541–6551

    Article  CAS  PubMed  Google Scholar 

  • Skulachev VP (1988) In: The sodium world. Membrane Bioenergetics. Springer-Verlag, Berlin, pp 293–326

  • Steuber J (2003) The C-terminally truncated NuoL subunit (ND5 homologue) of the Na+-dependent complex I from Escherichia coli transports Na+. J Biol Chem 278:26817–26822

    Article  CAS  PubMed  Google Scholar 

  • Steuber J, Schmid C, Rufibach M, Dimroth P (2000) Na+ translocation by complex I (NADH:quinone oxidoreductase) of Escherichia coli. Mol Microbiol 35:428–434

    Article  CAS  PubMed  Google Scholar 

  • Stolpe S, Friedrich T (2004) The Escherichia coli NADH:ubiquinone oxidoreductase (complex I) is a primary proton pump but may be capable of secondary sodium antiport. J Biol Chem 279:18377–18383

    Article  CAS  PubMed  Google Scholar 

  • Sturr MG, Guffanti AA, Krulwich TA (1994) Growth and bioenergetics of alkaliphilic Bacillus firmus OF4 in continuous culture at high pH. J Bacteriol 176:3111–3116

    CAS  PubMed  Google Scholar 

  • Swartz TH, Ito M, Hicks DB, Nuqui M, Guffanti AA, Krulwich TA (2005) The Mrp Na+/H+ antiporter increases the activity of the malate:quinone oxidoreductase of an Escherichia coli respiratory mutant. J Bacteriol 187:388–391

    Article  CAS  PubMed  Google Scholar 

  • Vijaranakul U, Nadakavukaren MJ, Bayles DO, Wilkinson BJ, Jayaswal RK (1997) Characterization of an NaCl-sensitive Staphylococcus aureus mutant and rescue of the NaCl-sensitive phenotype by glycine betaine but not by other compatible solutes. Appl Environ Microbiol 63:1889–1897

    CAS  PubMed  Google Scholar 

  • Wallace BJ, Young IG (1977) Aerobic respiration in mutants of Escherichia coli accumulating quinone analogues of ubiquinone. Biochim Biophys Acta 461:75–83

    CAS  PubMed  Google Scholar 

  • Wei Y et al. (2003) Mutational loss of a K+ and NH +4 transporter affects the growth and endospore formation of alkaliphilic Bacillus pseudofirmus OF4. J Bacteriol 185:5133–5147

    Article  CAS  PubMed  Google Scholar 

  • West IC, Mitchell P (1974) Proton/sodium ion antiport in Escherichia coli. Biochem J 144:87–90

    CAS  PubMed  Google Scholar 

  • Wiegert T, Homuth G, Versteeg S, Schumann W (2001) Alkaline shock induces the Bacillus subtilis sigmaW regulon. Mol Microbiol 41:59–71

    Google Scholar 

  • Yagi T, Matsuno-Yagi A (2003) The proton-translocating NADH-quinone oxidoreductase in the respiratory chain: the secret unlocked. Biochemistry 42:2266–2274

    Article  CAS  PubMed  Google Scholar 

  • Yoshinaka T, Takasu H, Tomizawa R, Kosona S, Kudo T (2003) A shaE deletion mutant showed lower Na+ sensitivity compared to other deletion mutants in the Bacillus subtilis sodium/hydrogen antiporter (Sha) system). J Biosci Bioeng 95:306–309

    CAS  Google Scholar 

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Acknowledgments

This work was supported in part by research grants from the Kurata Memorial Foundation for Promoting Science and a grant-in-aid for scientific research from the Ministry of Education, Science and Culture of Japan to M.I. and research grant GM28454 from the National Institutes of Health to T.A.K.

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Authors and Affiliations

  1. Department of Pharmacology & Biological Chemistry, Mount Sinai School of Medicine, Box 1603, 1 G. Levy Place, New York, NY, 10029, USA

    Talia H. Swartz & Terry Ann Krulwich

  2. Faculty of Life Sciences, Toyo University, Oura-gun, Gunma, 374-0193, Japan

    Sayuri Ikewada, Osamu Ishikawa & Masahiro Ito

Authors
  1. Talia H. Swartz
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  2. Sayuri Ikewada
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  3. Osamu Ishikawa
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  4. Masahiro Ito
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  5. Terry Ann Krulwich
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Correspondence to Terry Ann Krulwich.

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Communicated by K. Horikoshi

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Swartz, T.H., Ikewada, S., Ishikawa, O. et al. The Mrp system: a giant among monovalent cation/proton antiporters?. Extremophiles 9, 345–354 (2005). https://doi.org/10.1007/s00792-005-0451-6

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