Noncontact dipole effects on channel permeation. I. Experiments with (5F-indole)Trp13 gramicidin A channels.

Gramicidin A (gA), with four Trp residues per monomer, has an increased conductance compared to its Phe replacement analogs. When the dipole moment of the Trp13 side chain is increased by fluorination at indole position 5 (FgA), the conductance is expected to increase further. gA and FgA conductances to Na+, K+, and H+ were measured in planar diphytanoylphosphatidylcholine (DPhPC) or glycerylmonoolein (GMO) bilayers. In DPhPC bilayers, Na+ and K+ conductances increased upon fluorination, whereas in GMO they decreased. The low ratio in the monoglyceride bilayer was not reversed in GMO-ether bilayers, solvent-inflated or -deflated bilayers, or variable fatty acid chain monoglyceride bilayers. In both GMO and DPhPC bilayers, fluorination decreased conductance to H+ but increased conductance in the mixed solution, 1 M KCl at pH 2.0, where K+ dominates conduction. Eadie-Hofstee plot slopes suggest similar destabilization of K+ binding in both lipids. Channel lifetimes were not affected by fluorination in either lipid. These observations indicate that fluorination does not change the rotameric conformation of the side chain. The expected difference in the rate-limiting step for transport through channels in the two bilayers qualitatively explains all of the above trends.

[1]  D. Busath,et al.  Synthesis and channel properties of [Tau 16]gramicidin A. , 1989, Biochimica et biophysica acta.

[2]  D. Downing,et al.  Amyloid fibrils may be assembled from beta-helical protofibrils. , 1998, Biochemistry.

[3]  D. Busath,et al.  Photolysis of gramicidin A channels in lipid bilayers , 1983 .

[4]  J. Killian,et al.  Phase separation and hexagonal HII phase formation by gramicidins A, B and C in dioleoylphosphatidylcholine model membranes. A study on the role of the tryptophan residues. , 1987, Biochimica et biophysica acta.

[5]  T. Cross,et al.  Tryptophan hydrogen bonding and electric dipole moments: functional roles in the gramicidin channel and implications for membrane proteins. , 1995, Biochemistry.

[6]  K. C. Lee,et al.  Tryptophans in membrane proteins: indole ring orientations and functional implications in the gramicidin channel. , 1993, Biochemistry.

[7]  W. Hubbell,et al.  The membrane dipole potential in a total membrane potential model. Applications to hydrophobic ion interactions with membranes. , 1986, Biophysical journal.

[8]  L. B. Weiss,et al.  Resolution of linear gramicidins by preparative reversed-phase high-performance liquid chromatography , 1981 .

[9]  M. Karplus,et al.  Ion transport in the gramicidin channel: free energy of the solvated right-handed dimer in a model membrane , 1993 .

[10]  Joshua Jortner,et al.  Transport Through Membranes: Carriers, Channels and Pumps , 1988 .

[11]  N. Van Mau,et al.  Single channels and surface potential of linear gramicidins. , 1989, Biochimie.

[12]  J. Killian,et al.  Influence of lipid/peptide hydrophobic mismatch on the thickness of diacylphosphatidylcholine bilayers. A 2H NMR and ESR study using designed transmembrane alpha-helical peptides and gramicidin A. , 1998, Biochemistry.

[13]  C. Branden,et al.  Introduction to protein structure , 1991 .

[14]  T. McIntosh,et al.  Magnitude of the solvation pressure depends on dipole potential. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Busath,et al.  The use of physical methods in determining gramicidin channel structure and function. , 1993, Annual review of physiology.

[16]  F. Heitz,et al.  Analysis of the ion transfer through the channel of 9,11,13,15-phenylalanylgramicidin A. , 1986, Biophysical chemistry.

[17]  Randal R Ketchem,et al.  High-resolution polypeptide structure in a lamellar phase lipid environment from solid state NMR derived orientational constraints. , 1997, Structure.

[18]  T. Cross,et al.  Tryptophan dynamics and structural refinement in a lipid bilayer environment: solid state NMR of the gramicidin channel. , 1995, Biochemistry.

[19]  O. Andersen.  Ion movement through gramicidin A channels. Interfacial polarization effects on single-channel current measurements. , 1983, Biophysical journal.

[20]  M. Sancho,et al.  Electrostatic modeling of dipole-ion interactions in gramicidinlike channels. , 1991, Biophysical journal.

[21]  C. Etchebest,et al.  Linear Gramicidins : Influence of the Nature of the Aromatic Side Chains of the Channel Conductance , 1988 .

[22]  J. Sandblom,et al.  Electrical Behavior of Single-Filing Channels , 1983 .

[23]  R. Benz,et al.  The adsorption of phloretin to lipid monolayers and bilayers cannot be explained by langmuir adsorption isotherms alone. , 1998, Biophysical journal.

[24]  I. Tasaki,et al.  Structure and Function in Excitable Cells , 1983, Springer US.

[25]  J. Dilger.  The thickness of monoolein lipid bilayers as determined from reflectance measurements. , 1981, Biochimica et biophysica acta.

[26]  C. Giessner-Prettre,et al.  Experimental and quantum-chemical studies of the dipole moments of quinoline and indole , 1970 .

[27]  L. B. Weiss,et al.  Single-channel studies on linear gramicidins with altered amino acid side chains. Effects of altering the polarity of the side chain at position 1 in gramicidin A. , 1986, Biophysical journal.

[28]  E. Bamberg,et al.  Single-channel parameters of gramicidin A,B, and C. , 1976, Biochimica et biophysica acta.

[29]  D. Busath,et al.  Gramicidin tryptophans mediate formamidinium-induced channel stabilization. , 1995, Biophysical journal.

[30]  S. Hladky,et al.  Ion Movements in Gramicidin Channels , 1984 .

[31]  Peter C. Jordan,et al.  Electrostatic modeling of ion pores. Multipolar sources. , 1987, Biophysical chemistry.

[32]  F. Heitz,et al.  Gramicidin A analogs: influence of the substitution of the tryptophans by naphthylalanines. , 1989, Biochimie.

[33]  O. Andersen,et al.  Potential energy barriers to ion transport within lipid bilayers. Studies with tetraphenylborate. , 1975, Biophysical journal.

[34]  G. Szabó,et al.  Gramicidin forms multi-state rectifying channels , 1981, Nature.

[35]  Peter C. Jordan,et al.  A dipolar chain model for the electrostatics of transmembrane ion channels , 1991 .

[36]  D. Deamer,et al.  Proton conductance by the gramicidin water wire. Model for proton conductance in the F1F0 ATPases? , 1991, Biophysical journal.

[37]  S. Hladky,et al.  Membrane conductance and surface potential , 1973 .

[38]  S. Hladky,et al.  Ion movements in gramicidin pores. An example of single-file transport. , 1980, Biochimica et biophysica acta.

[39]  H. Brockman,et al.  Dipole potential of lipid membranes. , 1994, Chemistry and physics of lipids.

[40]  C. Venkatachalam,et al.  Theoretical conformational analysis of the Gramicidin a transmembrane channel. I. Helix sense and energetics of head‐to‐head dimerization , 1983 .

[41]  D. Haydon,et al.  Surface charge, surface dipoles and membrane conductance. , 1973, Biochimica et biophysica acta.

[42]  G. Szabó,et al.  Planar bilayer membranes from pure lipids. , 1979, Biochimica et biophysica acta.

[43]  I. Harada,et al.  Environments and conformations of tryptophan side chains of gramicidin A in phospholipid bilayers studied by Raman spectroscopy. , 1990, Biochemistry.

[44]  Peter C. Jordan.  Electrostatic modeling of ion pores. II. Effects attributable to the membrane dipole potential. , 1983, Biophysical journal.

[45]  H. V. Van Wart,et al.  Solid-phase peptide synthesis and solid-state NMR spectroscopy of [Ala3-15N][Val1]gramicidin A. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[46]  B. Chait,et al.  The structure of the potassium channel: molecular basis of K+ conduction and selectivity. , 1998, Science.

[47]  G. Szabó,et al.  Low conductance gramicidin A channels are head-to-head dimers of beta 6.3-helices. , 1988, Biophysical journal.

[48]  O. Andersen,et al.  Molecular determinants of channel function. , 1992, Physiological reviews.

[49]  P McGill,et al.  Boundary conditions for- single-ion diffusion. , 1996, Biophysical journal.

[50]  B. Hille,et al.  Potassium channels as multi-ion single-file pores , 1978, The Journal of general physiology.

[51]  V A Parsegian,et al.  Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces. , 1992, Biophysical journal.

[52]  F. Heitz,et al.  How can the aromatic side-chains modulate the conductance of the gramicidin channel? A new approach using non-coded amino acids. , 2009, International journal of peptide and protein research.

[53]  S. Hladky,et al.  The kinetics of ion movements in the gramicidin channel. , 1978, Federation proceedings.

[54]  H. Sullivan.  Ionic Channels of Excitable Membranes, 2nd Ed. , 1992, Neurology.

[55]  Single-salt behavior of a symmetrical 4-site channel with barriers at its middle and ends , 1984 .

[56]  F. Heitz,et al.  Single channels of 9, 11, 13, 15-destryptophyl-phenylalanyl-gramicidin A. , 1982, Biophysical journal.

[57]  O. Andersen,et al.  Gramicidin channels that have no tryptophan residues. , 1992, Biochemistry.

[58]  M. Yoder,et al.  Unusual structural features in the parallel β-helix in pectate lyases , 1993 .

[59]  F J Sigworth,et al.  Estimation of Na+ dwell time in the gramicidin A channel. Na+ ions as blockers of H+ currents. , 1989, Biochimica et biophysica acta.

[60]  S. Hladky,et al.  Ion transfer across lipid membranes in the presence of gramicidin A. I. Studies of the unit conductance channel. , 1972, Biochimica et biophysica acta.

[61]  O. Andersen,et al.  Amino acid sequence modulation of gramicidin channel function: effects of tryptophan-to-phenylalanine substitutions on the single-channel conductance and duration. , 1991, Biochemistry.

[62]  R. Koeppe,et al.  Orientations of the tryptophan 9 and 11 side chains of the gramicidin channel based on deuterium nuclear magnetic resonance spectroscopy. , 1994, Biophysical journal.

[63]  O. Andersen,et al.  Importance of Tryptophan Dipoles for Protein Function: 5-Fluorination of Tryptophans in Gramicidin A Channels , 1998 .

[64]  M. Goulian,et al.  Energetics of inclusion-induced bilayer deformations. , 1998, Biophysical journal.

[65]  G. Fields,et al.  Solid phase peptide synthesis of 15N-gramicidins A, B, and C and high performance liquid chromatographic purification. , 2009, International journal of peptide and protein research.

[66]  O. Andersen,et al.  Distinction between dipolar and inductive effects in modulating the conductance of gramicidin channels. , 1990, Biochemistry.

[67]  B. Roux,et al.  The binding site of sodium in the gramicidin A channel: comparison of molecular dynamics with solid-state NMR data. , 1997, Biophysical journal.

[68]  D. Marsh.  CRC handbook of lipid bilayers , 1990 .

[69]  E. Neher,et al.  Interactions in cation permeation through the gramicidin channel. Cs, Rb, K, Na, Li, Tl, H, and effects of anion binding. , 1978, Biophysical journal.

[70]  P. R. Bevington,et al.  Data Reduction and Error Analysis for the Physical Sciences , 1969 .

[71]  B. Hille.  Ionic channels of excitable membranes , 2001 .