Skip to main content
SpringerLink
Log in

Ion conductance vs. pore gating and selectivity in KcsA channel: Modeling achievements and perspectives

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

KcsA potassium channel belongs to a wide family of allosteric proteins that switch between closed and open states conformations in response to a stimulus, and act as a regulator of cation activity in living cells. The gating mechanism and cation selectivity of such channels have been extensively studied in the literature, with a revival emphasis these latter years, due to the publication of the crystallized structure of KcsA. Despite the increasing number of research and review papers on these topics, quantitative interpretation of these processes at the atomic scale is far from achieved. On the basis of available experimental and theoretical data, and by including our recent results, we review the progresses in this field of activity and discuss the weaknesses that should be corrected. In this spirit, we partition the channel into the filter, cavity, extra and intracellular media, in order to analyze separately the specificity of each region. Special emphasis is brought to the study of an open state for the channel and to the different properties generated by the opening. The influence of water as a structural and dynamical component of the channel properties in closed and open states, as well as in the sequential motions of the cations, is analyzed using molecular dynamics simulations and ab initio calculations. The polarization and charge transfer effects on the ions’ dynamics and kinetics are discussed in terms of partial charge models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15

Similar content being viewed by others

References

  1. Armstrong CM (1969) J Gen Physiol 54:553–575

    CAS  Google Scholar 

  2. Doyle DA, Cabral JM, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL et al (1998) Science 280:69–77

    CAS  Google Scholar 

  3. Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R (2002) Nature 417:515–522

    CAS  Google Scholar 

  4. Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R (2002) Nature 417:523–526

    CAS  Google Scholar 

  5. Cortes DM, Cuello LG, Perozo E (2001) J Gen Physiol 117:165–180

    CAS  Google Scholar 

  6. Yellen G (2002) Nature 419:35–42

    CAS  Google Scholar 

  7. Jiang Y, Lee A, Chen J, Ruta V, Cadene M, Chait BT, MacKinnon R (2003) Nature 423:33–41

    CAS  Google Scholar 

  8. Bernèche S, Roux B (2005) Structure 13:591–600

    Google Scholar 

  9. Cordero-Morales JF, Cuello LG, Perozo E (2006) Nat Struct Mol Biol 13:319–322

    CAS  Google Scholar 

  10. Cordero-Morales JF, Cuello LG, Zhao Y, Jogini V, Cortes DM, Roux B, Perozo E (2006) Nat Struct Mol Biol 13:311–318

    CAS  Google Scholar 

  11. Kuruta HT, Fedida D (2006) Biophys Mol Biol 92:185–208

    Google Scholar 

  12. Doyle DA (2004) Trends Neurosci 27:298–302

    CAS  Google Scholar 

  13. Swartz KJ (2004) Nat Struct Mol Biol 11:499–502

    CAS  Google Scholar 

  14. Chandler WK, Meves H (1965) J Physiol 180:788–820

    CAS  Google Scholar 

  15. Meves H, Chandler WK (1965) J Gen Physiol 48:31–33

    CAS  Google Scholar 

  16. Bezanilla F, Armstrong CM (1972) J Gen Physiol 60:588–608

    CAS  Google Scholar 

  17. Hille B (1973) J Gen Physiol 61:669–686

    CAS  Google Scholar 

  18. Allen TW, Hoyles M, Kuyucak S, Chung SH (1999) Chem Phys Lett 313:358–365

    CAS  Google Scholar 

  19. Allen TW, Bliznyuk A, Rendell AP, Kuyucak S, Chung SH (2000) J Chem Phys 112:8191–8204

    CAS  Google Scholar 

  20. Biggin PC, Smith GR, Shrivastava I, Choe S, Sansom MSP (2001) Biochim Biophys Acta 1510:1–9

    CAS  Google Scholar 

  21. Shrivastava IH, Tieleman DP, Biggin PC, Sansom MSP (2002) Biophys J 83:633–645

    CAS  Google Scholar 

  22. Domene C, Sansom MSP (2003) Biophys J 85:2787–2800

    CAS  Google Scholar 

  23. Guidoni L, Torre V, Carloni P (1999) Biochemistry 38:8599–8604

    CAS  Google Scholar 

  24. Olsson MHM, Mavri J, Warshel A (2006) Philos Trans R Soc Lond B 361:1417–1432

    CAS  Google Scholar 

  25. Braun-Sand S, Burykin A, Tao Chu Z, Warshel A (2005) J Phys Chem B 109:583–592

    CAS  Google Scholar 

  26. Luzhkov VB, Åqvist J (2005) Biochim Biophys Acta 1747:109–120

    CAS  Google Scholar 

  27. Bernèche S, Roux B (2001) Nature 414:73–77

    Google Scholar 

  28. MacKinnon R (2003) FEBS Lett 555:62–65

    CAS  Google Scholar 

  29. Gulbis J, Doyle DA (2004) Curr Opin Struct Biol 14:440–446

    CAS  Google Scholar 

  30. Korn SJ, Trapani JG (2005) IEEE Trans Nanobio 4:21–33

    Google Scholar 

  31. Sansom MSP, Shrivastava IH, Ranatunga KM, Smith GR (2000) Trends Biochem Sci 25:368–374

    CAS  Google Scholar 

  32. Chung SH, Kuyucak S (2002) Biochim Biophys Acta 1565:267–286

    CAS  Google Scholar 

  33. Sansom MSP, Shrivastava IH, Bright JN, Tate J, Capener CE, Biggin PC (2002) Biochim Biophys Acta 1565:294–307

    CAS  Google Scholar 

  34. Miloshevsky GV, Jordan PC (2004) TRENDS Neurosci 27:308–314

    CAS  Google Scholar 

  35. Roux B (2005) Annu Rev Biophys Biomol Struct 34:153–171

    CAS  Google Scholar 

  36. Roux B (2002) Curr Opin Struct Biol 12:182–189

    CAS  Google Scholar 

  37. Jogini V, Roux B (2005) J Mol Biol 354:272–288

    CAS  Google Scholar 

  38. Zhou Y, Morais-Cabral JH, Kaufman A, Mackinnon R (2001) Nature 414:43–48

    CAS  Google Scholar 

  39. Heginbotham L, Abramson T, MacKinnon R (1992) Science 258:1152–1155

    CAS  Google Scholar 

  40. Heginbotham L, Lu Z, Abramson T, MacKinnon R (1994) Biophys J 66:1061–1067

    CAS  Google Scholar 

  41. Nimigean CM, Chappie JS, Miller C (2003) Biochemistry 42:9263–9268

    CAS  Google Scholar 

  42. Chapman ML, Krovetz HS, VanDongen AMJ (2001) J Physiol 530:21–33

    CAS  Google Scholar 

  43. Hodgkin AL, Keynes RD (1955) J Physiol 128:61–88

    CAS  Google Scholar 

  44. Zhou Y, MacKinnon R (2003) J Mol Biol 333:965–975

    CAS  Google Scholar 

  45. Zhou M, MacKinnon R (2004) J Mol Biol 338:839–846

    CAS  Google Scholar 

  46. Roux B, Allen T, Bernèche S, Im W (2004) Q Rev Biophys 37:15–103

    CAS  Google Scholar 

  47. Guidoni L, Carloni P (2002) Biochim Biophys Acta 1563:1–6

    CAS  Google Scholar 

  48. Blizniuk AA, Rendell AP (2004) J Phys Chem B 108:13866–13873

    Google Scholar 

  49. Compoint M, Ramseyer C, Huetz P (2004) Chem Phys Lett 397:510–515

    CAS  Google Scholar 

  50. Huetz P, Boiteux C, Compoint M, Ramseyer C, Girardet C (2006) J Chem Phys 124:44703–44712

    Google Scholar 

  51. Bucher D, Raugei S, Guidoni L, Dal Peraro M, Rothlisberger U, Carloni P, Klein ML (2006) Biophys Chem 124:292–301

    CAS  Google Scholar 

  52. Roux B, Bernèche S, Im W (2000) Biochemistry 39:13295–13306

    Google Scholar 

  53. Case DA, Darden TA, Cheatham TE III, Simmerling CL, Wang J, Duke RE, Luo R, Merz KM, Wang B, Pearlman DA, Crowley M, Brozell S, Tsui V, Gohlke H, Mongan J, Hornak V, Cui G, Broza P, Schafmeister C, Caldwell JW, Ross WS, Kollman PA (2004) AMBER 8. University of California, San Francisco

    Google Scholar 

  54. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) J Comp Chem 4:187–217

    CAS  Google Scholar 

  55. Bekker H, Berendsen HJC, Dijkstra FJ, Achterop S, van Drunen R, van der Spoel D, Sijbers A, Keegstra H, Reitsma B, Renardus MKR (1993) Gromacs: A parallel computer for molecular dynamics simulations In: de Groot RA, Nadrchal J (eds) Physics computing 92, World Scientific, Singapore

    Google Scholar 

  56. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kale L, Schulten K (2005) J Comp Chem 26:1781–1802

    CAS  Google Scholar 

  57. Holyoake J, Domene C, Bright JN, Sansom MSP (2004) Eur Biophys J 33:238–246

    CAS  Google Scholar 

  58. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery Jr JA, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PM W, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2004) Gaussian 03, Revision C02, Gaussian, Wallingford CT

    Google Scholar 

  59. Åqvist J, Luzhkov V (2000) Nature 404:881–884

    Google Scholar 

  60. Morais-Cabral JH, Zhou Y, MacKinnon R (2001) Nature 414:37–40

    CAS  Google Scholar 

  61. Bernèche S, Roux B (2003) Proc Natl Acad Sci USA 100:8644–8648

    Google Scholar 

  62. Perozo E, Cortes DM, Cuello LG (1999) Science 285:73–78

    CAS  Google Scholar 

  63. Allen TW, Chung SH (2001) Biochim Biophys Acta 1515:83–91

    CAS  Google Scholar 

  64. Chung SH, Allen TW, Kuyucak S (2002) Biophys J 82:628–645

    CAS  Google Scholar 

  65. Biggin PC, Sansom MSP (2002) Biophys J 83:1867–1876

    CAS  Google Scholar 

  66. Shrivastava IH, Sansom MSP (2002) Eur Biophys J 31:207–216

    CAS  Google Scholar 

  67. Shen Y, Kong Y, Ma J (2002) Proc Natl Acad Sci USA 99:1949–1953

    Google Scholar 

  68. Grottesi A, Domene C, Haider S, Sansom MSP (2005) IEEE Trans Nanobio 4:112–120

    Google Scholar 

  69. Compoint M, Picaud F, Ramseyer C, Girardet, C (2005) J Chem Phys 122:134707–134715

    Google Scholar 

  70. Liu YS, Sompornpisut P, Perozo E (2001) Nat Struct Biol 8:883–887

    CAS  Google Scholar 

  71. Compoint M, Picaud F, Ramseyer C, Girardet C (2005) Chem Phys Lett 407:199–204

    CAS  Google Scholar 

  72. Guidoni L, Torre V, Carloni P (2000) FEBS Lett 477:37–42

    CAS  Google Scholar 

  73. Compoint M, Boiteux C, Huetz P, Ramseyer C, Girardet C (2005) Phys Chem Chem Phys 7:4138–4145

    CAS  Google Scholar 

  74. Green ME (2002) J Biomol Struct Dyn 19:725–730

    CAS  Google Scholar 

  75. Sapronova A, Bystrov V, Green ME (2003) Theochem 630:297–307

    CAS  Google Scholar 

  76. Bernèche S, Roux B (2002) Biophys J 82:772–780

    Google Scholar 

  77. VanDongen AMJ (2004) Proc Natl Acad Sci USA 101:3248–3252

    Google Scholar 

  78. Bernèche S, Roux B (2000) Biophys J 78:2900–2917

    Article  Google Scholar 

  79. Nelson PH (2002) J Chem Phys 117:11396–11403

    CAS  Google Scholar 

  80. Mafé S, Pellicer J, Cervera J (2005) J Chem Phys 122:204712–204720

    Google Scholar 

  81. Yesylevskyy SO, Kharkyanen VN (2004) Phys Chem Chem Phys 6:3111–3122

    CAS  Google Scholar 

  82. Kraszewski S, Boiteux C, Langner M, Ramseyer C (2006) Phys Chem Chem Phys 9:1219–1225

    Google Scholar 

  83. Boiteux C, Compoint M, Huetz P, Ramseyer C, Girardet C (2005) IEJMD 4:1–14

    Google Scholar 

  84. Compoint M, Carloni P, Ramseyer C, Girardet C (2004) Biochim Biophys Acta 1661:26–39

    CAS  Google Scholar 

  85. Consiglio JF, Andalib P, Korn SJ (2003) J Gen Physiol 121:111–124

    CAS  Google Scholar 

  86. Beckstein O, Sansom MSP (2003) Proc Natl Acad Sci USA 100:7063–7068

    Google Scholar 

  87. Saparov SM, Pohl P (2004) Proc Natl Acad Sci USA 101:4805–4809

    Google Scholar 

  88. Roux B, MacKinnon R (1999) Science 285:100–102

    CAS  Google Scholar 

  89. Senapati S, Chandra A (2001) J Phys Chem B 105:5106–5109

    CAS  Google Scholar 

  90. Molina ML, Encinar JA, Barrera FN, Fernandez-Ballester G, Riquelme G, Gonzalez-Ros JM (2004) Biochemistry 43:14924–14931

    CAS  Google Scholar 

  91. Encinar JA, Molina ML, Poveda JA, Barrera FN, Renart ML, Fernandez AM, Gonzalez-Ros JM (2004) FEBS Lett 579:5199–5204

    Google Scholar 

  92. Corry B, Vora T, Chung SH (2005) Biochim Biophys Acta 1711:72–86

    CAS  Google Scholar 

  93. Corry B, Chung SH (2006) Cell Mol Life Sci 63:301–315

    CAS  Google Scholar 

  94. Luzhkov VB, Åqvist J (2001) Biochim Biophys Acta 1548:194–202

    CAS  Google Scholar 

  95. Nimigean CM, Miller C (2002) J Gen Physiol 120:323–335

    CAS  Google Scholar 

  96. Bichet D, Grabe M, Jan YN, Jan LY (2006) Proc Natl Acad Sci USA 103:14355–14360

    Google Scholar 

  97. Noskov SY, Bernèche S, Roux B (2004) Nature 431:830–834

    CAS  Google Scholar 

  98. Shi N, Ye S, Alam A, Chen L, Jiang Y (2006) Nature 440:570–574

    CAS  Google Scholar 

  99. Asthagiri D, Pratt R, Paulaitis ME (2006) J Chem Phys 125:24701–24707

    CAS  Google Scholar 

  100. Ban F, Kusalik P, Weaver DF (2004) J Am Chem Soc 126:4711–4716

    CAS  Google Scholar 

  101. Singh UC, Kollman PA (1984) J Comp Chem 5:129–145

    CAS  Google Scholar 

  102. Besler BH, Merz KM, Kollman PA (1990) J Comp Chem 11:431–439

    CAS  Google Scholar 

  103. Hinsen K, Roux B (1997) J Comp Chem 18:368–380

    CAS  Google Scholar 

  104. Zhou Y, MacKinnon R (2004) Biochemistry 43:4978–4982

    CAS  Google Scholar 

  105. LeMasurier M, Heginbotham L, Miller C (2001) J Gen Physiol 118:303–313

    CAS  Google Scholar 

  106. Treptow W, Tarek M (2006) Biophys J 91:L26–L28

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Physique Moléculaire UMR CNRS 6624, Université de Franche-Comté, La Bouloie, 25030, Besançon Cedex, France

    Céline Boiteux, Sebastian Kraszewski, Christophe Ramseyer & Claude Girardet

Authors
  1. Céline Boiteux
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sebastian Kraszewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christophe Ramseyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claude Girardet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claude Girardet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boiteux, C., Kraszewski, S., Ramseyer, C. et al. Ion conductance vs. pore gating and selectivity in KcsA channel: Modeling achievements and perspectives. J Mol Model 13, 699–713 (2007). https://doi.org/10.1007/s00894-007-0202-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00894-007-0202-y

Keywords

Search

Navigation