Cited by 189Bacterial Genetics and BiotechnologyIon channel regulation and functionIon Transport and Channel Regulation

Molecular Mechanisms for Bacterial Potassium Homeostasis

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Stautz, Janina, Hellmich, Yvonne, Fuss, Michael F., Silberberg, Jakob M., Devlin, Jason R., Stockbridge, Randy B., Hänelt, Inga·2021·Journal of Molecular Biology

Abstract

Potassium ion homeostasis is essential for bacterial survival, playing roles in osmoregulation, pH homeostasis, regulation of protein synthesis, enzyme activation, membrane potential adjustment and electrical signaling. To accomplish such diverse physiological tasks, it is not surprising that a single bacterium typically encodes several potassium uptake and release systems. To understand the role each individual protein fulfills and how these proteins work in concert, it is important to identify the molecular details of their function. One needs to understand whether the systems transport ions actively or passively, and what mechanisms or ligands lead to the activation or inactivation of individual systems. Combining mechanistic information with knowledge about the physiology under different stress situations, such as osmostress, pH stress or nutrient limitation, one can identify the task of each system and deduce how they are coordinated with each other. By reviewing the general principles of bacterial membrane physiology and describing the molecular architecture and function of several bacterial K+-transporting systems, we aim to provide a framework for microbiologists studying bacterial potassium homeostasis and the many K+-translocating systems that are still poorly understood.

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  • At equilibrium, free metal pools are significant for K+ and Mg2+ and are composed of both free and weakly complexed ions.

    “At equilibrium, free metal pools are significant for K+ and Mg2+ and are composed of both free and weakly complexed ions.5−7”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [7]

    The Introduction section on K+ transport and equilibrium ion distributions (page unavailable) describes substantial intracellular K+ concentrations and how K+ distributes across the membrane at equilibrium. It does not establish a significant free Mg2+ pool or say that either pool comprises both free and weakly complexed ions. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • K+ maintains osmotic balance and is an important contributor to the membrane potential.

    “This dominant cation maintains osmotic balance7,46,47 and is an important contributor to the membrane potential.48”
  • Most bacteria have total concentrations (quotas) of >100 mM for the bulk ions K+ and Mg2+.

    “with most bacteria having total concentrations (quotas) of >100 mM.7−9”

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  1. [1]Benarroch JM, Asally M. The Microbiologist’s Guide to Membrane Potential Dynamics. Trends Microbiol. 2020; 28: 304– 14. 31952908
  2. [2]Beagle SD, Lockless SW. Unappreciated Roles for K(+) Channels in Bacterial Physiology. Trends Microbiol. 2020. PMC9159956 33288383
  3. [3]Zhou M, Morais-Cabral JH, Mann S, MacKinnon R. Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors. Nature. 2001; 411: 657– 61. 11395760
  4. [4]Fan C, Sukomon N, Flood E, Rheinberger J, Allen TW, Nimigean CM. Ball-and-chain inactivation in a calcium-gated potassium channel. Nature. 2020; 580: 288– 93. 32269335 PMC7153497
  5. [6]Cao Y, Pan Y, Huang H, Jin X, Levin EJ, Kloss B, Gating of the TrkH ion channel by its associated RCK protein TrkA. Nature. 2013; 496: 317– 22. 23598339 PMC3726529
  6. [7]Huang CS, Pedersen BP, Stokes DL. Crystal structure of the potassium-importing KdpFABC membrane complex. Nature. 2017; 546: 681– 5. 28636601 PMC5495170
  7. [8]Tascon I, Sousa JS, Corey RA, Mills DJ, Griwatz D, Aumuller N, Structural basis of proton-coupled potassium transport in the KUP family. Nat Commun. 2020; 11: 626. 32005818 PMC6994465
  8. [9]Poolman B, Konings WN. Secondary solute transport in bacteria. Biochim Biophys Acta. 1993; 1183: 5– 39. 8399376
  9. [10]Zilberstein D, Schuldiner S, Padan E. Proton electrochemical gradient in Escherichia coli cells and its relation to active transport of lactose. Biochemistry. 1979; 18: 669– 73. 33700
  10. [11]Felle H, Porter JS, Slayman CL, Kaback HR. Quantitative measurements of membrane potential in Escherichia coli. Biochemistry. 1980; 19: 3585– 90. 6996707
  11. [12]Milo R, Phillips R. Cell biology by the numbers. New York, NY: Garland Science, Taylor & Francis Group. 2016.
  12. [15]Martinac B, Saimi Y, Kung C. Ion channels in microbes. Physiol Rev. 2008; 88: 1449– 90. 18923187 PMC2579964
  13. [16]Epstein W The roles and regulation of potassium in bacteria. Prog Nucleic Acid Res Mol Biol. 2003; 75: 293– 320. 14604015
  14. [17]Nissen P, Hansen J, Ban N, Moore PB, Steitz TA. The structural basis of ribosome activity in peptide bond synthesis. Science. 2000; 289: 920– 30. 10937990
  15. [18]Mm Kuo, Haynes WJ Loukin SH, Kung C, Saimi Y. Prokaryotic K(+) channels: from crystal structures to diversity. FEMS Microbiol Rev. 2005; 29: 961– 85. 16026885
  16. [19]Kuo MM, Saimi Y, Kung C. Gain-of-function mutations indicate that Escherichia coli Kch forms a functional K+ conduit in vivo. EMBO J. 2003; 22: 4049– 58. 12912904 PMC175798
  17. [20]Stock C, Hielkema L, Tascon I, Wunnicke D, Oostergetel GT, Azkargorta M, Cryo-EM structures of KdpFABC suggest a K(+) transport mechanism via two inter-subunit half-channels. Nat Commun. 2018; 9: 4971. 30478378 PMC6255902
  18. [21]Schlösser A, Meldorf M, Stumpe S, Bakker EP, Epstein W. TrkH and its homolog, TrkG, determine the specificity and kinetics of cation transport by the Trk system of Escherichia coli. J Bacteriol. 1995; 177: 1908– 10. 7896723 PMC176828
  19. [22]Dosch DC, Helmer GL, Sutton SH, Salvacion FF, Epstein W. Genetic analysis of potassium transport loci in Escherichia coli: evidence for three constitutive systems mediating uptake potassium. J Bacteriol. 1991; 173: 687– 96. 1987159 PMC207060
  20. [23]Kirichok Y, Krapivinsky G, Clapham DE. The mitochondrial calcium uniporter is a highly selective ion channel. Nature. 2004; 427: 360– 4. 14737170
  21. [24]Bernardi P Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev. 1999; 79: 1127– 55. 10508231
  22. [25]Ji C, Stockbridge RB, Miller C. Bacterial fluoride resistance, Fluc channels, and the weak acid accumulation effect. J Gen Physiol. 2014; 144: 257– 61. 25156118 PMC4144673
  23. [26]Stockbridge RB, Robertson JL, Kolmakova-Partensky L, Miller C. A family of fluoride-specific ion channels with dual-topology architecture. Elife. 2013; 2:e01084. PMC3755343 23991286
  24. [28]Wisniewski JR, Rakus D. Multi-enzyme digestion FASP and the ‘Total Protein Approach’-based absolute quantification of the Escherichia coli proteome. J Proteomics. 2014; 109: 322– 31. 25063446
  25. [29]Papanastasiou M, Orfanoudaki G, Kountourakis N, Koukaki M, Sardis MF, Aivaliotis M, Rapid label-free quantitative analysis of the E. coli BL21(DE3) inner membrane proteome. Proteomics. 2016; 16: 85– 97. 26466526
  26. [30]Borisov VB, Murali R, Verkhovskaya ML, Bloch DA, Han H, Gennis RB, Aerobic respiratory chain of Escherichia coli is not allowed to work in fully uncoupled mode. Proc Natl Acad Sci U S A. 2011; 108: 17320– 4. 21987791 PMC3198357
  27. [31]Szenk M, Dill KA, de Graff AMR. Why Do Fast-Growing Bacteria Enter Overflow Metabolism? Testing the Membrane Real Estate Hypothesis. Cell Syst. 2017; 5: 95– 104. 28755958
  28. [32]Cuello LG, Jogini V, Cortes DM, Perozo E. Structural mechanism of C-type inactivation in K(+) channels. Nature. 2010; 466: 203– 8. 20613835 PMC3033749
  29. [33]Humphries J, Xiong L, Liu J, Prindle A, Yuan F, Arjes HA, Species-Independent Attraction to Biofilms through Electrical Signaling. Cell. 2017; 168:200–9 e12. PMC5497501 28086091
  30. [35]Bruni GN, Kralj JM. Membrane voltage dysregulation driven by metabolic dysfunction underlies bactericidal activity of aminoglycosides. Elife. 2020; 9. PMC7406350 32748785
  31. [36]Bryan LE, Kwan S. Roles of ribosomal binding, membrane potential, and electron transport in bacterial uptake of streptomycin and gentamicin. Antimicrob Agents Chemother. 1983; 23: 835– 45. 6351731 PMC184978
  32. [37]Stratford JP, Edwards CLA, Ghanshyam MJ, Malyshev D, Delise MA, Hayashi Y, Electrically induced bacterial membrane-potential dynamics correspond to cellular proliferation capacity. Proc Natl Acad Sci U S A. 2019; 116: 9552– 7. 31000597 PMC6511025
  33. [38]Zhang H, Pan Y, Hu L, Hudson MA, Hofstetter KS, Xu Z, TrkA undergoes a tetramer-to-dimer conversion to open TrkH which enables changes in membrane potential. Nat Commun. 2020; 11: 547. 31992706 PMC6987127
  34. [39]Ochrombel I, Ott L, Krämer R, Burkovski A, Marin K. Impact of improved potassium accumulation on pH homeostasis, membrane potential adjustment and survival of Corynebacterium glutamicum. Biochim Biophys Acta. 2011; 1807: 444– 50. 21295539
  35. [40]Prindle A, Liu J, Asally M, Ly S, Garcia-Ojalvo J, Suel GM. Ion channels enable electrical communication in bacterial communities. Nature. 2015; 527: 59– 63. 26503040 PMC4890463
  36. [41]Kashket ER, Barker SL. Effects of potassium ions on the electrical and pH gradients across the membrane of Streptococcus lactis cells. J Bacteriol. 1977; 130: 1017– 23. 16864 PMC235322
  37. [42]Booth IR. Regulation of cytoplasmic pH in bacteria. Microbiol Rev. 1985; 49: 359– 78. 3912654 PMC373043
  38. [43]Xue T, You Y, Hong D, Sun H, Sun B. The Staphylococcus aureus KdpDE two-component system couples extracellular K+ sensing and Agr signaling to infection programming. Infect Immun. 2011; 79: 2154– 67. 21422185 PMC3125826
  39. [44]MacGilvary NJ, Kevorkian YL, Tan S. Potassium response and homeostasis in Mycobacterium tuberculosis modulates environmental adaptation and is important for host colonization. PLoS Pathog. 2019; 15:e1007591. PMC6375644 30716121
  40. [45]Liu J, Prindle A, Humphries J, Gabalda-Sagarra M, Asally M, Lee DY, Metabolic co-dependence gives rise to collective oscillations within biofilms. Nature. 2015; 523: 550– 4. 26200335 PMC4862617
  41. [46]Martinez-Corral R, Liu J, Prindle A, Suel GM, Garcia-Ojalvo J. Metabolic basis of brain-like electrical signalling in bacterial communities. Philos Trans R Soc Lond B Biol Sci. 2019; 374:20180382. PMC6553584 31006362
  42. [47]Kralj JM, Hochbaum DR, Douglass AD, Cohen AE. Electrical spiking in Escherichia coli probed with a fluorescent voltage-indicating protein. Science. 2011; 333: 345– 8. 21764748
  43. [48]Bruni GN, Weekley RA, Dodd BJT, Kralj JM. Voltage-gated calcium flux mediates Escherichia coli mechanosensation. Proc Natl Acad Sci U S A. 2017; 114: 9445– 50. 28808010 PMC5584419
  44. [49]Sirec T, Benarroch JM, Buffard P, Garcia-Ojalvo J, Asally M. Electrical Polarization Enables Integrative Quality Control during Bacterial Differentiation into Spores. iScience. 2019; 16: 378– 89. 31226599 PMC6586994
  45. [50]Stingl K, Brandt S, Uhlemann EM, Schmid R, Altendorf K, Zeilinger C, Channel-mediated potassium uptake in Helicobacter pylori is essential for gastric colonization. EMBO J. 2007; 26: 232– 41. 17159901 PMC1782367
  46. [51]Follmann M, Becker M, Ochrombel I, Ott V, Krämer R, Marin K. Potassium transport in Corynebacterium glutamicum is facilitated by the putative channel protein CglK, which is essential for pH homeostasis and growth at acidic pH. J Bacteriol. 2009; 191: 2944– 52. 19270097 PMC2681794
  47. [52]Ungar D, Barth A, Haase W, Kaunzinger A, Lewitzki E, Ruiz T, Analysis of a putative voltage-gated prokaryotic potassium channel. Eur J Biochem. 2001; 268: 5386– 96. 11606201
  48. [53]Schrempf H, Schmidt O, Kummerlen R, Hinnah S, Muller D, Betzler M, A prokaryotic potassium ion channel with two predicted transmembrane segments from Streptomyces lividans. EMBO J. 1995; 14: 5170– 8. 7489706 PMC394625
  49. [54]Hirano M, Onishi Y, Yanagida T, Ide T. Role of the KcsA channel cytoplasmic domain in pH-dependent gating. Biophys J. 2011; 101: 2157– 62. 22067153 PMC3207171
  50. [55]Xu Y, McDermott AE. Inactivation in the potassium channel KcsA. J Struct Biol X. 2019; 3:100009. PMC7337057 32647814
  51. [56]Baker KA, Tzitzilonis C, Kwiatkowski W, Choe S, Riek R. Conformational dynamics of the KcsA potassium channel governs gating properties. Nat Struct Mol Biol. 2007; 14: 1089– 95. 17922011 PMC3525321
  52. [57]Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science. 1998; 280: 69– 77. 9525859
  53. [58]Morais-Cabral JH, Zhou Y, MacKinnon R. Energetic optimization of ion conduction rate by the K+ selectivity filter. Nature. 2001; 414: 37– 42. 11689935
  54. [59]Zhou Y, Morais-Cabral JH, Kaufman A, MacKinnon R. Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution. Nature. 2001; 414: 43– 8. 11689936
  55. [60]Öster C, Hendriks K, Kopec W, Chevelkov V, Shi C, Michl D, The conduction pathway of potassium channels is water free under physiological conditions. Sci Adv. 2019; 5:eaaw6756. PMC6669007 31392272
  56. [61]Köpfer DA, Song C, Gruene T, Sheldrick GM, Zachariae U, de Groot BL. Ion permeation in K(+) channels occurs by direct Coulomb knock-on. Science. 2014; 346: 352– 5. 25324389
  57. [62]Kopec W, Köpfer DA, Vickery ON, Bondarenko AS, Jansen TLC, de Groot BL, Direct knock-on of desolvated ions governs strict ion selectivity in K(+) channels. Nat Chem. 2018; 10: 813– 20. 30030538
  58. [63]Cuello LG, Cortes DM, Perozo E. The gating cycle of a K(+) channel at atomic resolution. Elife. 2017; 6. PMC5711375 29165243
  59. [64]Cordero-Morales JF, Cuello LG, Zhao Y, Jogini V, Cortes DM, Roux B, Molecular determinants of gating at the potassium-channel selectivity filter. Nat Struct Mol Biol. 2006; 13: 311– 8. 16532009
  60. [65]Valiyaveetil FI, Leonetti M, Muir TW, Mackinnon R. Ion selectivity in a semisynthetic K+ channel locked in the conductive conformation. Science. 2006; 314: 1004– 7. 17095703
  61. [66]Schrecker M, Wunnicke D, Hanelt I. How RCK domains regulate gating of K+ channels. Biol Chem. 2019; 400: 1303– 22. 31361596
  62. [67]Albright RA, Ibar JL, Kim CU, Gruner SM, Morais-Cabral JH. The RCK domain of the KtrAB K+ transporter: multiple conformations of an octameric ring. Cell. 2006; 126: 1147– 59. 16990138
  63. [68]Jiang Y, Pico A, Cadene M, Chait BT, MacKinnon R. Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel. Neuron. 2001; 29: 593– 601. 11301020
  64. [69]Rao ST, Rossmann MG. Comparison of super-secondary structures in proteins. J Mol Biol. 1973; 76: 241– 56. 4737475
  65. [70]Roosild TP, Miller S, Booth IR, Choe S. A mechanism of regulating transmembrane potassium flux through a ligand-mediated conformational switch. Cell. 2002; 109: 781– 91. 12086676
  66. [71]Kong C, Zeng W, Ye S, Chen L, Sauer DB, Lam Y, Distinct gating mechanisms revealed by the structures of a multi-ligand gated K(+) channel. Elife. 2012; 1:e00184. PMC3510474 23240087
  67. [72]Kröning N, Willenborg M, Tholema N, Hänelt I, Schmid R, Bakker EP. ATP binding to the KTN/RCK subunit KtrA from the K+ -uptake system KtrAB of Vibrio alginolyticus: its role in the formation of the KtrAB complex and its requirement in vivo. J Biol Chem. 2007; 282:14018–27. 17344221
  68. [73]Tamsett TJ, Picchione KE, Bhattacharjee A. NAD+ activates KNa channels in dorsal root ganglion neurons. J Neurosci. 2009; 29: 5127– 34. 19386908 PMC6665483
  69. [74]Corrigan RM, Campeotto I, Jeganathan T, Roelofs KG, Lee VT, Grundling A. Systematic identification of conserved bacterial c-di-AMP receptor proteins. Proc Natl Acad Sci U S A. 2013; 110: 9084– 9. 23671116 PMC3670340
  70. [75]Kim H, Youn SJ, Kim SO, Ko J, Lee JO, Choi BS. Structural Studies of Potassium Transport Protein KtrA Regulator of Conductance of K+ (RCK) C Domain in Complex with Cyclic Diadenosine Monophosphate (c-di-AMP). J Biol Chem. 2015; 290: 16393– 402. 25957408 PMC4481236
  71. [76]Hite RK, Yuan P, Li Z, Hsuing Y, Walz T, MacKinnon R. Cryo-electron microscopy structure of the Slo2.2 Na(+)-activated K(+) channel. Nature. 2015; 527: 198– 203. 26436452 PMC4886347
  72. [77]Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R. Crystal structure and mechanism of a calcium-gated potassium channel. Nature. 2002; 417: 515– 22. 12037559
  73. [78]Kuo MM, Maslennikov I, Molden B, Choe S. The desensitization gating of the MthK K+ channel is governed by its cytoplasmic amino terminus. PLoS Biol. 2008; 6: e223. 18959476 PMC2573919
  74. [79]Pau VP, Abarca-Heidemann K, Rothberg BS. Allosteric mechanism of Ca2+ activation and H+-inhibited gating of the MthK K+ channel. J Gen Physiol. 2010; 135: 509– 26. 20421375 PMC2860591
  75. [80]Li Y, Berke I, Chen L, Jiang Y. Gating and inward rectifying properties of the MthK K+ channel with and without the gating ring. J Gen Physiol. 2007; 129: 109– 20. 17261840 PMC2154359
  76. [81]Boiteux C, Posson DJ, Allen TW, Nimigean CM. Selectivity filter ion binding affinity determines inactivation in a potassium channel. Proc Natl Acad Sci USA. 2020; 117:29968–78. PMC7703589 33154158
  77. [82]Holtmann G, Bakker EP, Uozumi N, Bremer E. KtrAB and KtrCD: two K+ uptake systems in Bacillus subtilis and their role in adaptation to hypertonicity. J Bacteriol. 2003; 185: 1289– 98. 12562800 PMC142857
  78. [83]Nakamura T, Yuda R, Unemoto T, Bakker EP. KtrAB, a new type of bacterial K(+)-uptake system from Vibrio alginolyticus. J Bacteriol. 1998; 180: 3491– 4. 9642210 PMC107312
  79. [84]Matsuda N, Kobayashi H, Katoh H, Ogawa T, Futatsugi L, Nakamura T, Na+-dependent K+ uptake Ktr system from the cyanobacterium Synechocystis sp. PCC 6803 and its role in the early phases of cell adaptation to hyperosmotic shock. J Biol Chem. 2004; 279: 54952– 62. 15459199
  80. [85]Rhoads DB, Epstein W. Energy coupling to net K+ transport in Escherichia coli K-12. J Biol Chem. 1977; 252: 1394– 401. 320207
  81. [86]Tholema N, Vor der Brüggen M, Mäser P, Nakamura T, Schroeder JI, Kobayashi H, All four putative selectivity filter glycine residues in KtrB are essential for high affinity and selective K+ uptake by the KtrAB system from Vibrio alginolyticus. J Biol Chem. 2005; 280:41146–54. 16210320
  82. [87]Mikusevic V, Schrecker M, Kolesova N, Patino-Ruiz M, Fendler K, Hänelt I. A channel profile report of the unusual K(+) channel KtrB. J Gen Physiol. 2019; 151: 1357– 68. 31624134 PMC6888753
  83. [88]Hänelt I, Tholema N, Kröning N, Vor der Brüggen M, Wunnicke D, Bakker EP. KtrB, a member of the superfamily of K+ transporters. Eur J Cell Biol. 2011; 90: 696– 704. 21680052
  84. [89]Corratge-Faillie C, Jabnoune M, Zimmermann S, Very AA, Fizames C, Sentenac H. Potassium and sodium transport in non-animal cells: the Trk/Ktr/HKT transporter family. Cell Mol Life Sci. 2010; 67: 2511– 32. 20333436 PMC11115768
  85. [90]Cao Y, Jin X, Huang H, Derebe MG, Levin EJ, Kabaleeswaran V, Crystal structure of a potassium ion transporter, TrkH. Nature. 2011; 471: 336– 40. PMC3077569 21317882
  86. [91]Sr Durell, Hao Y, Nakamura T Bakker EP, Guy HR Evolutionary relationship between K(+) channels and symporters. Biophysical Journal. 1999; 77: 775– 88. 10423425 PMC1300371
  87. [92]Tholema N, Bakker EP, Suzuki A, Nakamura T. Change to alanine of one out of four selectivity filter glycines in KtrB causes a two orders of magnitude decrease in the affinities for both K+ and Na+ of the Na+ dependent K+ uptake system KtrAB from Vibrio alginolyticus. FEBS Lett. 1999; 450: 217– 20. 10359077
  88. [93]Levin EJ, Zhou M. Recent progress on the structure and function of the TrkH/KtrB ion channel. Curr Opin Struct Biol. 2014; 27: 95– 101. 25011047 PMC4182332
  89. [94]Hänelt I, Wunnicke D, Müler-Trimbusch M, Vor der Brüggen M, Kraus I, Bakker EP, Membrane region M2C2 in subunit KtrB of the K+ uptake system KtrAB from Vibrio alginolyticus forms a flexible gate controlling K+ flux: an electron paramagnetic resonance study. J Biol Chem. 2010; 285:28210–9. PMC2934686 20573964
  90. [95]Hänelt I, Löchte S, Sundermann L, Elbers K, Vor der Brüggen M, Bakker EP. Gain of function mutations in membrane region M2C2 of KtrB open a gate controlling K+ transport by the KtrAB system from Vibrio alginolyticus. J Biol Chem. 2010; 285:10318–27. PMC2856237 20097755
  91. [96]Vieira-Pires RS, Szollosi A, Morais-Cabral JH. The structure of the KtrAB potassium transporter. Nature. 2013; 496: 323– 8. 23598340
  92. [97]Zhou M, MacKinnon R. A mutant KcsA K(+) channel with altered conduction properties and selectivity filter ion distribution. J Mol Biol. 2004; 338: 839– 46. 15099749
  93. [98]Derebe MG, Sauer DB, Zeng W, Alam A, Shi N, Jiang Y. Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites. Proc Natl Acad Sci U S A. 2011; 108: 598– 602. 21187421 PMC3021048
  94. [99]Szollosi A, Vieira-Pires RS, Teixeira-Duarte CM, Rocha R, Morais-Cabral JH. Dissecting the Molecular Mechanism of Nucleotide-Dependent Activation of the KtrAB K+ Transporter. PLoS Biol. 2016; 14:e1002356. PMC4714889 26771197
  95. [100]Diskowski M, Mehdipour AR, Wunnicke D, Mills DJ, Mikusevic V, Bärland N, Helical jackknives control the gates of the double-pore K(+) uptake system KtrAB. Elife. 2017; 6. PMC5449183 28504641
  96. [101]Teixeira-Duarte CM, Fonseca F, Morais-Cabra JH Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site. Elife. 2019; 8. PMC6957272 31868587
  97. [102]Rocha R, Teixeira-Duarte CM, Jorge JMP, Morais-Cabral JH. Characterization of the molecular properties of KtrC, a second RCK domain that regulates a Ktr channel in Bacillus subtilis. J Struct Biol. 2019; 205: 34– 43. 30753894
  98. [103]Stulke J, Kruger L. Cyclic di-AMP Signaling in Bacteria. Annu Rev Microbiol. 2020; 74: 159– 79. 32603625
  99. [104]Chakrapani S, Perozo E. How to gate an ion channel: lessons from MthK. Nat Struct Mol Biol. 2007; 14: 180– 2. 17334406
  100. [105]Pedersen BP, Stokes DL, Apell HJ. The KdpFABC complex – K(+) transport against all odds. Mol Membr Biol. 2019; 35: 21– 38. 31259644 PMC6681667
  101. [106]Durell SR, Bakker EP, Guy HR. Does the KdpA subunit from the high affinity K(+)- translocating P-type KDP-ATPase have a structure similar to that of K(+) channels? Biophysical Journal. 2000; 78: 188– 99. 10620285 PMC1300629
  102. [107]Schrader M, Fendler K, Bamberg E, Gassel M, Epstein W, Altendorf K, Replacement of glycine 232 by aspartic acid in the KdpA subunit broadens the ion specificity of the K(+)-translocating KdpFABC complex. Biophys J. 2000; 79: 802– 13. 10920013 PMC1300979
  103. [108]van der Laan M, Gassel M, Altendorf K. Characterization of amino acid substitutions in KdpA, the K+-binding and -translocating subunit of the KdpFABC complex of Escherichia coli. J Bacteriol. 2002; 184: 5491– 4. 12218037 PMC135338
  104. [109]Buurman ET, Kim KT, Epstein W. Genetic evidence for two sequentially occupied K+ binding sites in the Kdp transport ATPase. J Biol Chem. 1995; 270: 6678– 85. 7896809
  105. [110]Becker D, Fendler K, Altendorf K, Greie JC. The conserved dipole in transmembrane helix 5 of KdpB in the Escherichia coli KdpFABC P-type ATPase is crucial for coupling and the electrogenic K+-translocation step. Biochemistry. 2007; 46:13920–8. 17994765
  106. [111]Albers RW. Biochemical aspects of active transport. Annu Rev Biochem. 1967; 36: 727– 56. 18257736
  107. [112]Post RL, Hegyvary C, Kume S. Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. J Biol Chem. 1972; 247: 6530– 40. 4263199
  108. [113]Post RL, Kume S. Evidence for an aspartyl phosphate residue at the active site of sodium and potassium ion transport adenosine triphosphatase. J Biol Chem. 1973; 248: 6993– 7000. 4270326
  109. [114]Puppe W, Siebers A, Altendorf K. The phosphorylation site of the Kdp-ATPase of Escherichia coli: site-directed mutagenesis of the aspartic acid residues 300 and 307 of the KdpB subunit. Mol Microbiol. 1992; 6: 3511– 20. 1474895
  110. [115]Bramkamp M, Altendorf K. Single amino acid substitution in the putative transmembrane helix V in KdpB of the KdpFABC complex of Escherichia coli uncouples ATPase activity and ion transport. Biochemistry. 2005; 44: 8260– 6. 15938615
  111. [116]Gassel M, Möllenkamp T, Puppe W, Altendorf K. The KdpF subunit is part of the K(+)-translocating Kdp complex of Escherichia coli and is responsible for stabilization of the complex in vitro. J Biol Chem. 1999; 274: 37901– 7. 10608856
  112. [117]Bramkamp M, Altendorf K, Greie JC. Common patterns and unique features of P-type ATPases: a comparative view on the KdpFABC complex from Escherichia coli (Review). Mol Membr Biol. 2007; 24: 375– 86. 17710642
  113. [118]Gassel M, Altendorf K. Analysis of KdpC of the K(+)-transporting KdpFABC complex of Escherichia coli. Eur J Biochem. 2001; 268: 1772– 81. 11248697
  114. [119]Shull GE, Lane LK, Lingrel JB. Amino-acid sequence of the beta-subunit of the (Na+ + K+)ATPase deduced from a cDNA. Nature. 1986; 321: 429– 31. 3012356
  115. [120]Axelsen KB, Palmgren MG. Evolution of substrate specificities in the P-type ATPase superfamily. J Mol Evol. 1998; 46: 84– 101. 9419228
  116. [121]Biology Kühlbrandt W., structure and mechanism of P-type ATPases. Nat Rev Mol Cell Biol. 2004; 5: 282– 95. 15071553
  117. [122]Greie JC, Altendorf K. The K+-translocating KdpFABC complex from Escherichia coli: a P-type ATPase with unique features. J Bioenerg Biomembr. 2007; 39: 397– 402. 18058005
  118. [123]Damnjanovic B, Weber A, Potschies M, Greie JC, Apell HJ. Mechanistic analysis of the pump cycle of the KdpFABC P-type ATPase. Biochemistry. 2013; 52: 5563– 76. 23930894
  119. [124]Schramke H, Tostevin F, Heermann R, Gerland U, Jung K. A Dual-Sensing Receptor Confers Robust Cellular Homeostasis. Cell Rep. 2016; 16: 213– 21. 27320909
  120. [125]Laermann V, Cudic E, Kipschull K, Zimmann P, Altendorf K. The sensor kinase KdpD of Escherichia coli senses external K+. Mol Microbiol. 2013; 88: 1194– 204. 23651428
  121. [126]Sweet ME, Zhang X, Erdjument-Bromage H, Dubey V, Khandelia H, Neubert TA, Serine phosphorylation regulates the P-type potassium pump KdpFABC. Elife. 2020; 9. PMC7535926 32955430
  122. [127]Trchounian A, Kobayashi H. Kup is the major K+ uptake system in Escherichia coli upon hyper-osmotic stress at a low pH. FEBS Lett. 1999; 447: 144– 8. 10214935
  123. [128]Schleyer M, Bakker EP. Nucleotide sequence and 3’-end deletion studies indicate that the K(+)-uptake protein Kup from Escherichia coli is composed of a hydrophobic core linked to a large and partially essential hydrophilic C terminus. J Bacteriol. 1993; 175: 6925– 31. 8226635 PMC206818
  124. [129]Vastermark A, Wollwage S, Houle ME, Rio R, Saier MH, Jr. Expansion of the APC superfamily of secondary carriers. Proteins. 2014; 82: 2797– 811. 25043943 PMC4177346
  125. [130]Zakharyan E, Trchounian A. K+ influx by Kup in Escherichia coli is accompanied by a decrease in H+ efflux. FEMS Microbiol Lett. 2001; 204: 61– 4. 11682179
  126. [131]Izard T The crystal structures of phosphopantetheine adenylyltransferase with bound substrates reveal the enzyme’s catalytic mechanism. J Mol Biol. 2002; 315: 487– 95. 11812124
  127. [132]Gundlach J, Krüger L, Herzberg C, Turdiev A, Poehlein A, Tascon I, Sustained sensing in potassium homeostasis: Cyclic di-AMP controls potassium uptake by KimA at the levels of expression and activity. J Biol Chem. 2019. PMC6579464 31061098
  128. [133]Quintana IM, Gibhardt J, Turdiev A, Hammer E, Commichau FM, Lee VT, The KupA and KupB proteins of Lactococcus lactis IL1403 are novel c-di-AMP receptor proteins responsible for potassium uptake. J Bacteriol. 2019. PMC6482930 30745376
  129. [134]Pham HT, Turner MS. Onward and [K(+)]Upward: a New Potassium Importer under the Spell of Cyclic di-AMP. J Bacteriol. 2019; 201. PMC6482924 30858295
  130. [135]Epstein W, Kim BS. Potassium transport loci in Escherichia coli K-12. J Bacteriol. 1971; 108: 639– 44. 4942756 PMC247121
  131. [136]Sukharev SI, Blount P, Martinac B, Blattner FR, Kung C. A large-conductance mechanosensitive channel in E. coli encoded by mscL alone. Nature. 1994; 368: 265– 8. 7511799
  132. [137]Bakker EP, Booth IR, Dinnbier U, Epstein W, Gajewska A. Evidence for multiple K+ export systems in Escherichia coli. J Bacteriol. 1987; 169: 3743– 9. 3301813 PMC212460
  133. [138]Roosild TP, Castronovo S, Healy J, Miller S, Pliotas C, Rasmussen T, Mechanism of ligand-gated potassium efflux in bacterial pathogens. Proc Natl Acad Sci U S A. 2010; 107:19784–9. PMC2993342 21041667
  134. [139]Gundlach J, Herzberg C, Kaever V, Gunka K, Hoffmann T, Weiss M, Control of potassium homeostasis is an essential function of the second messenger cyclic di-AMP in Bacillus subtilis. Sci Signal. 2017; 10. 28420751
  135. [140]Fujisawa M, Ito M, Krulwich TA. Three two-component transporters with channel-like properties have monovalent cation/proton antiport activity. Proc Natl Acad Sci U S A. 2007; 104:13289–94. PMC1948933 17679694
  136. [141]Krüger L, Herzberg C, Warneke R, Poehlein A, Stautz J, Weiss M, Two ways to convert a low- to a high-affinity potassium channel: Control of Bacillus subtilis KtrCD by glutamate. J Bacteriol. 2020. PMC7253608 32253343
  137. [142]Liu J, Martinez-Corral R, Prindle A, Lee DD, Larkin J, Gabalda-Sagarra M, Coupling between distant biofilms and emergence of nutrient time-sharing. Science. 2017; 356: 638– 42. 28386026 PMC5645014
  138. [143]Su J, Gong H, Lai J, Main A, Lu S. The potassium transporter Trk and external potassium modulate Salmonella enterica protein secretion and virulence. Infect Immun. 2009; 77: 667– 75. 19001074 PMC2632022
  139. [144]Liu Y, Ho KK, Su J, Gong H, Chang AC, Lu S. Potassium transport of Salmonella is important for type III secretion and pathogenesis. Microbiology. 2013; 159: 1705– 19. 23728623 PMC4089031
  140. [145]Price-Whelan A, Poon CK, Benson MA, Eidem TT, Roux CM, Boyd JM, Transcriptional profiling of Staphylococcus aureus during growth in 2 M NaCl leads to clarification of physiological roles for Kdp and Ktr K+ uptake systems. MBio. 2013; 4. PMC3747578 23963175
  141. [146]Gries CM, Bose JL, Nuxoll AS, Fey PD, Bayles KW. The Ktr potassium transport system in Staphylococcus aureus and its role in cell physiology, antimicrobial resistance and pathogenesis. Mol Microbiol. 2013; 89: 760– 73. 23815639 PMC3754831
  142. [147]Freeman ZN, Dorus S, Waterfield NR. The KdpD/KdpE two-component system: integrating K(+) homeostasis and virulence. PLoS Pathog. 2013; 9:e1003201. PMC3610689 23555240
  143. [148]Samir R, Hussein SH, Elhosseiny NM, Khattab MS, Shawky AE, Attia AS. Adaptation to Potassium-Limitation Is Essential for Acinetobacter baumannii Pneumonia Pathogenesis. J Infect Dis. 2016; 214: 2006– 13. 27923956
  144. [149]Yost S, Duran-Pinedo AE, Krishnan K, Frias-Lopez J. Potassium is a key signal in host-microbiome dysbiosis in periodontitis. PLoS Pathog. 2017; 13:e1006457. PMC5493431 28632755
  145. [150]Cortes DM, Cuello LG, Perozo E. Molecular architecture of full-length KcsA: role of cytoplasmic domains in ion permeation and activation gating. J Gen Physiol. 2001; 117: 165– 80. 11158168 PMC2217246
  146. [151]Ye S, Li Y, Chen L, Jiang Y. Crystal structures of a ligand-free MthK gating ring: insights into the ligand gating mechanism of K+ channels. Cell. 2006; 126: 1161– 73. 16990139
  147. [152]Gundlach J, Herzberg C, Hertel D, Thurmer A, Daniel R, Link H, Adaptation of Bacillus subtilis to Life at Extreme Potassium Limitation. MBio. 2017; 8. PMC5573677 28679749
  148. [153]Gibhardt J, Hoffmann G, Turdiev A, Wang M, Lee VT, Commichau FM. c-di-AMP assists osmoadaptation by regulating the Listeria monocytogenes potassium transporters KimA and KtrCD. J Biol Chem. 2019; 294:16020–33. PMC6827311 31506295
  149. [154]Watson PY, Fedor MJ. The ydaO motif is an ATP-sensing riboswitch in Bacillus subtilis. Nat Chem Biol. 2012; 8: 963– 5. 23086297
  150. [155]Sato Y, Nanatani K, Hamamoto S, Shimizu M, Takahashi M, Tabuchi-Kobayashi M, Defining membrane spanning domains and crucial membrane-localized acidic amino acid residues for K(+) transport of a Kup/HAK/KT-type Escherichia coli potassium transporter. J Biochem. 2014; 155: 315– 23. 24519967
  151. [156]Chin KH, Liang JM, Yang JG, Shih MS, Tu ZL, Wang YC, Structural Insights into the Distinct Binding Mode of Cyclic Di-AMP with SaCpaA_RCK. Biochemistry. 2015; 54: 4936– 51. 26171638
  152. [157]Chandrangsu P, Dusi R, Hamilton CJ, Helmann JD. Methylglyoxal resistance in Bacillus subtilis: contributions of bacillithiol-dependent and independent pathways. Mol Microbiol. 2014; 91: 706– 15. 24330391 PMC3945468
  153. [158]Fujisawa M, Wada Y, Ito M. Modulation of the K+ efflux activity of Bacillus subtilis YhaU by YhaT and the C-terminal region of YhaS. FEMS Microbiol Lett. 2004; 231: 211– 7. 14987767

Cited by

Sorted by citations

Authors
Stautz, J., Hellmich, Y., Fuss, M. F., Silberberg, J. M., Devlin, J. R., Stockbridge, R. B., & Hänelt, I.
Affiliations
  • Goethe University Frankfurt (DE)
  • University of Michigan (US)
Corresponding author
  • Stockbridge, Randy B.
  • Hänelt, Inga
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2021-08
Volume
433
Issue
16
Pages
166968
ISSN
0022-2836 (ISSN-L)
OpenAlex
W3146941526
Cited by
189
References
3
Citations by year
2026: 46 · 2025: 55 · 2024: 44 · 2023: 23 · 2022: 15 · 2021: 6
FWCI
3.29
Type
journal article
Language
en
Open access
Locations
  • Journal of Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
Deutsche Forschungsgemeinschaft (HA6322/3-1, HA6322/4-1, SFB 807)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
potassium transporters, osmoregulation, pH homeostasis, membrane potential, electrical signaling, osmostress, pH stress, nutrient limitation, membrane physiology
MeSH terms
Bacteria, Biological Transport, Homeostasis, Membrane Potentials, Potassium, Structure-Activity Relationship, Potassium Channels, Ion Transport, Bacterial Physiological Phenomena

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