Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1999 Nov;77(5):2492–2501. doi: 10.1016/S0006-3495(99)77085-2

Noncontact dipole effects on channel permeation. III. Anomalous proton conductance effects in gramicidin

LR Phillips 1, CD Cole 1, RJ Hendershot 1, M Cotten 1, TA Cross 1, DD Busath 1
PMCID: PMC1300525  PMID: 20540928

Abstract

Proton transport on water wires, of interest for many problems in membrane biology, is analyzed in side-chain analogs of gramicidin A channels. In symmetrical 0.1 N HCl solutions, fluorination of channel Trp(11), Trp-(13), or Trp(15) side chains is found to inhibit proton transport, and replacement of one or more Trps with Phe enhances proton transport, the opposite of the effects on K(+) transport in lecithin bilayers. The current-voltage relations are superlinear, indicating that some membrane field-dependent process is rate limiting. The interfacial dipole effects are usually assumed to affect the rate of cation translocation across the channel. For proton conductance, however, water reorientation after proton translocation is anticipated to be rate limiting. We propose that the findings reported here are most readily interpreted as the result of dipole-dipole interactions between channel waters and polar side chains or lipid headgroups. In particular, if reorientation of the water column begins with the water nearest the channel exit, this hypothesis explains the negative impact of fluorination and the positive impact of headgroup dipole on proton conductance.

Full Text

The Full Text of this article is available as a PDF (102.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akeson M., Deamer D. W. Proton conductance by the gramicidin water wire. Model for proton conductance in the F1F0 ATPases? Biophys J. 1991 Jul;60(1):101–109. doi: 10.1016/S0006-3495(91)82034-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersen O. S. Ion movement through gramicidin A channels. Single-channel measurements at very high potentials. Biophys J. 1983 Feb;41(2):119–133. doi: 10.1016/S0006-3495(83)84414-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bamberg E., Noda K., Gross E., Läuger P. Single-channel parameters of gramicidin A,B, and C. Biochim Biophys Acta. 1976 Jan 21;419(2):223–228. doi: 10.1016/0005-2736(76)90348-5. [DOI] [PubMed] [Google Scholar]
  4. Becker M. D., Greathouse D. V., Koeppe R. E., 2nd, Andersen O. S. Amino acid sequence modulation of gramicidin channel function: effects of tryptophan-to-phenylalanine substitutions on the single-channel conductance and duration. Biochemistry. 1991 Sep 10;30(36):8830–8839. doi: 10.1021/bi00100a015. [DOI] [PubMed] [Google Scholar]
  5. Bjerrum N. Structure and Properties of Ice. Science. 1952 Apr 11;115(2989):385–390. doi: 10.1126/science.115.2989.385. [DOI] [PubMed] [Google Scholar]
  6. Boyer P. D. The ATP synthase--a splendid molecular machine. Annu Rev Biochem. 1997;66:717–749. doi: 10.1146/annurev.biochem.66.1.717. [DOI] [PubMed] [Google Scholar]
  7. Busath D. D., Thulin C. D., Hendershot R. W., Phillips L. R., Maughan P., Cole C. D., Bingham N. C., Morrison S., Baird L. C., Hendershot R. J. Noncontact dipole effects on channel permeation. I. Experiments with (5F-indole)Trp13 gramicidin A channels. Biophys J. 1998 Dec;75(6):2830–2844. doi: 10.1016/S0006-3495(98)77726-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cotten M., Tian C., Busath D. D., Shirts R. B., Cross T. A. Modulating dipoles for structure-function correlations in the gramicidin A channel. Biochemistry. 1999 Jul 20;38(29):9185–9197. doi: 10.1021/bi982981m. [DOI] [PubMed] [Google Scholar]
  9. Cseh R., Benz R. The adsorption of phloretin to lipid monolayers and bilayers cannot be explained by langmuir adsorption isotherms alone. Biophys J. 1998 Mar;74(3):1399–1408. doi: 10.1016/S0006-3495(98)77852-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cukierman S., Quigley E. P., Crumrine D. S. Proton conduction in gramicidin A and in its dioxolane-linked dimer in different lipid bilayers. Biophys J. 1997 Nov;73(5):2489–2502. doi: 10.1016/S0006-3495(97)78277-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Daumas P., Heitz F., Ranjalahy-Rasoloarijao L., Lazaro R. Gramicidin A analogs: influence of the substitution of the tryptophans by naphthylalanines. Biochimie. 1989 Jan;71(1):77–81. doi: 10.1016/0300-9084(89)90135-1. [DOI] [PubMed] [Google Scholar]
  12. DeCoursey T. E., Cherny V. V. Voltage-activated hydrogen ion currents. J Membr Biol. 1994 Sep;141(3):203–223. doi: 10.1007/BF00235130. [DOI] [PubMed] [Google Scholar]
  13. Deamer D. W. Proton permeation of lipid bilayers. J Bioenerg Biomembr. 1987 Oct;19(5):457–479. doi: 10.1007/BF00770030. [DOI] [PubMed] [Google Scholar]
  14. Dorigo A. E., Anderson D. G., Busath D. D. Noncontact dipole effects on channel permeation. II. Trp conformations and dipole potentials in gramicidin A. Biophys J. 1999 Apr;76(4):1897–1908. doi: 10.1016/S0006-3495(99)77348-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eisenman G., Enos B., Hägglund J., Sandblom J. Gramicidin as an example of a single-filing ionic channel. Ann N Y Acad Sci. 1980;339:8–20. doi: 10.1111/j.1749-6632.1980.tb15964.x. [DOI] [PubMed] [Google Scholar]
  16. Eisenman G., Sandblom J., Neher E. Interactions in cation permeation through the gramicidin channel. Cs, Rb, K, Na, Li, Tl, H, and effects of anion binding. Biophys J. 1978 May;22(2):307–340. doi: 10.1016/S0006-3495(78)85491-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fields C. G., Fields G. B., Noble R. L., Cross T. A. Solid phase peptide synthesis of 15N-gramicidins A, B, and C and high performance liquid chromatographic purification. Int J Pept Protein Res. 1989 Apr;33(4):298–303. doi: 10.1111/j.1399-3011.1989.tb01285.x. [DOI] [PubMed] [Google Scholar]
  18. Fields G. B., Fields C. G., Petefish J., Van Wart H. E., Cross T. A. Solid-phase peptide synthesis and solid-state NMR spectroscopy of [Ala3-15N][Val1]gramicidin A. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1384–1388. doi: 10.1073/pnas.85.5.1384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fonseca V., Daumas P., Ranjalahy-Rasoloarijao L., Heitz F., Lazaro R., Trudelle Y., Andersen O. S. Gramicidin channels that have no tryptophan residues. Biochemistry. 1992 Jun 16;31(23):5340–5350. doi: 10.1021/bi00138a014. [DOI] [PubMed] [Google Scholar]
  20. Girvin M. E., Rastogi V. K., Abildgaard F., Markley J. L., Fillingame R. H. Solution structure of the transmembrane H+-transporting subunit c of the F1F0 ATP synthase. Biochemistry. 1998 Jun 23;37(25):8817–8824. doi: 10.1021/bi980511m. [DOI] [PubMed] [Google Scholar]
  21. Haydon D. A., Hladky S. B. Ion transport across thin lipid membranes: a critical discussion of mechanisms in selected systems. Q Rev Biophys. 1972 May;5(2):187–282. doi: 10.1017/s0033583500000883. [DOI] [PubMed] [Google Scholar]
  22. Heinemann S. H., Sigworth F. J. Estimation of Na+ dwell time in the gramicidin A channel. Na+ ions as blockers of H+ currents. Biochim Biophys Acta. 1989 Dec 11;987(1):8–14. doi: 10.1016/0005-2736(89)90448-3. [DOI] [PubMed] [Google Scholar]
  23. Heitz F., Gavach C., Spach G., Trudelle Y. Analysis of the ion transfer through the channel of 9,11,13,15-phenylalanylgramicidin A. Biophys Chem. 1986 Jul;24(2):143–148. doi: 10.1016/0301-4622(86)80007-2. [DOI] [PubMed] [Google Scholar]
  24. Heitz F., Spach G., Trudelle Y. Single channels of 9, 11, 13, 15-destryptophyl-phenylalanyl-gramicidin A. Biophys J. 1982 Oct;40(1):87–89. doi: 10.1016/S0006-3495(82)84462-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hille B., Schwarz W. Potassium channels as multi-ion single-file pores. J Gen Physiol. 1978 Oct;72(4):409–442. doi: 10.1085/jgp.72.4.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hladky S. B., Haydon D. A. Ion transfer across lipid membranes in the presence of gramicidin A. I. Studies of the unit conductance channel. Biochim Biophys Acta. 1972 Aug 9;274(2):294–312. doi: 10.1016/0005-2736(72)90178-2. [DOI] [PubMed] [Google Scholar]
  27. Hu W., Cross T. A. Tryptophan hydrogen bonding and electric dipole moments: functional roles in the gramicidin channel and implications for membrane proteins. Biochemistry. 1995 Oct 31;34(43):14147–14155. doi: 10.1021/bi00043a020. [DOI] [PubMed] [Google Scholar]
  28. Hu W., Lazo N. D., Cross T. A. Tryptophan dynamics and structural refinement in a lipid bilayer environment: solid state NMR of the gramicidin channel. Biochemistry. 1995 Oct 31;34(43):14138–14146. doi: 10.1021/bi00043a019. [DOI] [PubMed] [Google Scholar]
  29. Koeppe R. E., 2nd, Killian J. A., Greathouse D. V. Orientations of the tryptophan 9 and 11 side chains of the gramicidin channel based on deuterium nuclear magnetic resonance spectroscopy. Biophys J. 1994 Jan;66(1):14–24. doi: 10.1016/S0006-3495(94)80748-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Krasne S., Eisenman G. Influence of molecular variations of ionophore and lipid on the selective ion permeability of membranes: I. Tetranactin and the methylation of nonactin-type carriers. J Membr Biol. 1976 Dec 25;30(1):1–44. doi: 10.1007/BF01869658. [DOI] [PubMed] [Google Scholar]
  31. Lanyi J. K. Bacteriorhodopsin as a model for proton pumps. Nature. 1995 Jun 8;375(6531):461–463. doi: 10.1038/375461a0. [DOI] [PubMed] [Google Scholar]
  32. Levitt D. G., Elias S. R., Hautman J. M. Number of water molecules coupled to the transport of sodium, potassium and hydrogen ions via gramicidin, nonactin or valinomycin. Biochim Biophys Acta. 1978 Sep 22;512(2):436–451. doi: 10.1016/0005-2736(78)90266-3. [DOI] [PubMed] [Google Scholar]
  33. Läuger P. Diffusion-limited ion flow through pores. Biochim Biophys Acta. 1976 Dec 2;455(2):493–509. doi: 10.1016/0005-2736(76)90320-5. [DOI] [PubMed] [Google Scholar]
  34. Myers V. B., Haydon D. A. Ion transfer across lipid membranes in the presence of gramicidin A. II. The ion selectivity. Biochim Biophys Acta. 1972 Aug 9;274(2):313–322. doi: 10.1016/0005-2736(72)90179-4. [DOI] [PubMed] [Google Scholar]
  35. Nagle J. F., Morowitz H. J. Molecular mechanisms for proton transport in membranes. Proc Natl Acad Sci U S A. 1978 Jan;75(1):298–302. doi: 10.1073/pnas.75.1.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nagle J. F. Theory of passive proton conductance in lipid bilayers. J Bioenerg Biomembr. 1987 Oct;19(5):413–426. doi: 10.1007/BF00770027. [DOI] [PubMed] [Google Scholar]
  37. Nagle J. F., Tristram-Nagle S. Hydrogen bonded chain mechanisms for proton conduction and proton pumping. J Membr Biol. 1983;74(1):1–14. doi: 10.1007/BF01870590. [DOI] [PubMed] [Google Scholar]
  39. Peskoff A., Bers D. M. Electrodiffusion of ions approaching the mouth of a conducting membrane channel. Biophys J. 1988 Jun;53(6):863–875. doi: 10.1016/S0006-3495(88)83167-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Pnevmatikos S. Soliton dynamics of hydrogen-bonded networks: A mechanism for proton conductivity. Phys Rev Lett. 1988 Apr 11;60(15):1534–1537. doi: 10.1103/PhysRevLett.60.1534. [DOI] [PubMed] [Google Scholar]
  41. Pomès R., Roux B. Free energy profiles for H+ conduction along hydrogen-bonded chains of water molecules. Biophys J. 1998 Jul;75(1):33–40. doi: 10.1016/S0006-3495(98)77492-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Pomès R., Roux B. Structure and dynamics of a proton wire: a theoretical study of H+ translocation along the single-file water chain in the gramicidin A channel. Biophys J. 1996 Jul;71(1):19–39. doi: 10.1016/S0006-3495(96)79211-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Rosenberg P. A., Finkelstein A. Interaction of ions and water in gramicidin A channels: streaming potentials across lipid bilayer membranes. J Gen Physiol. 1978 Sep;72(3):327–340. doi: 10.1085/jgp.72.3.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sagnella D. E., Laasonen K., Klein M. L. Ab initio molecular dynamics study of proton transfer in a polyglycine analog of the ion channel gramicidin A. Biophys J. 1996 Sep;71(3):1172–1178. doi: 10.1016/S0006-3495(96)79321-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sagnella D. E., Voth G. A. Structure and dynamics of hydronium in the ion channel gramicidin A. Biophys J. 1996 May;70(5):2043–2051. doi: 10.1016/S0006-3495(96)79773-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sancho M., Martínez G. Electrostatic modeling of dipole-ion interactions in gramicidinlike channels. Biophys J. 1991 Jul;60(1):81–88. doi: 10.1016/S0006-3495(91)82032-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Seoh S. A., Busath D. Gramicidin tryptophans mediate formamidinium-induced channel stabilization. Biophys J. 1995 Jun;68(6):2271–2279. doi: 10.1016/S0006-3495(95)80409-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Tripathi S., Hladky S. B. Streaming potentials in gramicidin channels measured with ion-selective microelectrodes. Biophys J. 1998 Jun;74(6):2912–2917. doi: 10.1016/S0006-3495(98)77998-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Woolf T. B., Roux B. The binding site of sodium in the gramicidin A channel: comparison of molecular dynamics with solid-state NMR data. Biophys J. 1997 May;72(5):1930–1945. doi: 10.1016/S0006-3495(97)78839-8. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES