Energy profiles in the gramicidin A channel

Pullman, Alberte

doi:10.1017/s0033583500004170

Cited by 50 publications

(25 citation statements)

References 57 publications

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“…The planar lipid bilayer membrane as developed by Mueller et al (2) has proven to be remarkably useful as a model ofthe cell membrane. It was discovered that small ions cross these membranes by two mechanisms: ion channels that can be gated by voltage or receptors (3,4) and ion carriers that are not gated (5). We now show that the latter ionic currents, exemplified by currents of large hydrophobic ions, can be gated by photoinduced charge generation inside the membrane.…”

mentioning

confidence: 68%

Photogating of ionic currents across a lipid bilayer.

Drain

Christensen

Mauzerall

1989

Proc. Natl. Acad. Sci. U.S.A.

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Photoformation of metalloporphyrin cations in a lipid bilayer increases the ionic currents of negative and decreases those of positive hydrophobic ions. At low concentrations of the mobile hydrophobic ion, a 30% change in conductivity is observed that decreases with increasing concentration of positive tetraphenylphosphonium ion and increases drastically with increasing concentration of negative tetraphenylboride ion. In the region of saturated conductance of boride ion, the increase in conductivity is 3.6-fold. A 15-fold increase is observed with the protonophore carbonyl cyanide 3-chlorophenylhydrazone. In this case the net charge gated is 300 times greater than the photogenerated charge in the bilayer membrane. Thus there is a net gain in this organic field effect phototransistor. The gating can also be accomplished by continuous light or chemical oxidants. Photogating is explained as space charge effects inside the bilayer.There is great interest in the movement of ions across cell membranes since these currents are associated with the activity ofall metabolically functional cells. In addition, there is much work aimed at understanding the chemical properties ofthese membranes (1). The planar lipid bilayer membrane as developed by Mueller et al. (2) has proven to be remarkably useful as a model ofthe cell membrane. It was discovered that small ions cross these membranes by two mechanisms: ion channels that can be gated by voltage or receptors (3, 4) and ion carriers that are not gated (5). We now show that the latter ionic currents, exemplified by currents of large hydrophobic ions, can be gated by photoinduced charge generation inside the membrane. The photogating effect is explained by local electrostatic effects in the bilayer membrane. The pigment/ bilayer/hydrophobic ion system is an example of an organic field effect phototransistor (6).Much work has been carried out on the mechanism by which ion carriers or hydrophobic ions cross the lipid bilayer (7-11). The large radius of these ionic species decreases the Born electrostatic charging energy of the ion, thus enabling them to traverse the hydrocarbon core of the membrane (10). It is striking that for hydrophobic ions of similar size, the conductivity of negative ions is 102-103 times that of positive ions (7,8,12,13). This observation has been explained by a dipolar potential, originating in ordered ester carbonyl groups, which is positive toward the hydrocarbon core (12). Most studies of the kinetics of ion crossing monitor either current relaxations after an applied voltage step or voltage relaxations after a charge pulse (7,9). These techniques, although very useful, are limited by capacitive transients and by ambiguity of interpretation (14). The present technique avoids the former problem and allows a direct measure of the transients in the change of conductivity. EXPERIMENTALThe 4-ml plastic membrane cell was separated by a Teflon divider with a 1-mm2 hole in the center and had glass slides for windows. A bilayer was formed from a solut...

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mentioning

confidence: 68%

Photogating of ionic currents across a lipid bilayer.

Drain

Christensen

Mauzerall

1989

Proc. Natl. Acad. Sci. U.S.A.

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“…Previous reviews have addressed the experimentally observed permeability properties of gramicidin channels (1,10,48,54), the analysi s of peptide backbone structures (141,177), the use of NMR to estimate ion associati on and dissociation rates (169), the effect of gramicidin on lipids (40, 44), and progress on modeling the energetics of cation transport (80,81,118). Some of these topics are revisited with emphasis on subsequent work and new interpretations of older results.…”

Section: Introductionmentioning

confidence: 99%

“…This article reviews the determination of the molecular structure (second ary, tertiary, and quarternary) starting from the point where only the primary sequence was known. We first discuss the basis for early modeling as a {3 structure, the physical methods used to test the models, and the advantages and limitations of these older methods, and then review the most recent progress on structure and function.Previous reviews have addressed the experimentally observed permeability properties of gramicidin channels (1, 10, 48, 54), the analysi s of peptide backbone structures (141,177), the use of NMR to estimate ion associati on and dissociation rates (169), the effect of gramicidin on lipids (40, 44), and progress on modeling the energetics of cation transport (80, 81,118). Some of these topics are revisited with emphasis on subsequent work and new interpretations of older results.…”

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confidence: 99%

The Use of Physical Methods in Determining Gramicidin Channel Structure and Function

Busath

1993

Annu. Rev. Physiol.

124

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The various details provided by physical methods have been integrated into a coherent picture of the cation transport process. The free energy profile describes simultaneously the thermodynamic and kinetic factors that govern conductance. Localization of ion binding sites near each end of the channel by NMR and X-ray crystallographic techniques demonstrates that there is an energy barrier separating the two ends. There is no a priori reason to suspect any barrier to ion entry into the channel, and recent molecular modeling computations confirm this intuition. Therefore, the channel is best described as a two-site, one-barrier channel. However, the movement of ions across the central barrier over a distance of 1.9 nm is really a multistep process best described as Brownian motion (even the short steps from one pair of carbonyls to the next is more diffusive than activated for ions as large as Na+), the entry step is probably best considered as a compound step requiring correction for interfacial polarization and diffusion limitation, the binding sites in the channel ought not be considered to be in equilibrium with the bath, and quasi-knock off behavior (binding of a second ion at the entry facilitates release of a first ion from the exit) is probably the rule at physiological permeant ion concentrations and higher. Progress will probably focus on channel kinetics. The channel backbone probably undergoes conformational changes as the ions pass which, according to solid state NMR results, may last long enough to provide the channel with a sort of memory and which may give rise to excess single channel noise. These conformational changes are further reflected in shifts in side chain positions which, in turn, may be partly responsible for changes in the single-channel lifetime, which appears to be exquisitely sensitive to side chain-lipid interactions. Reasonable explanations for the impermeance of divalent cations, anions, and medium-sized organic cations such as guanidinium have proven elusive at first, but it now appears that divalent cations bind water too tightly, anions bind water in an orientation that produces unfavorable contacts between water oxygens and peptide carbonyl oxygens at the channel entry, and iminium ions bind strongly to the flexible peptide carbonyls at the channel entry.

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“…The number and the structuring of the water molecules in the channel in the absence of the ion are those determined previously and described in details in (6).The geometry adopted for the channel is, as in our previous papers (1)(2)(3)(4)(5)(6)(7)(8)(9), that of the head-to-head dimer proposed by Urry, each monomer being constructed with standard bond lengths and angles and with the phi, psi dihedral angles given in ref 16. The conformations of the side chains are those given as the most stable ones in (17).…”

Section: Methodsmentioning

confidence: 99%

“…In the previous papers (1)(2)(3)(4)(5)(6)(7)(8)(9) we have undertaken the study of the problem of ion transport in the Gramicidin A channel (GA) from a theoretical point of view by the computation of the "energy profile" felt by various cations progressing along the channel. We have focused our attention extensively on the case ofN a+ for which we have examined in detail the influence of the structural components of the channel and of the water molecules present at the mouth and in the channel on this profile.…”

Section: Introductionmentioning

confidence: 99%

Energy Profile of Cs⁺in Gramicidin A in the Presence of Water. Problem of the Ion Selectivity of the Channel

Etchebest

Pullman²

1988

Journal of Biomolecular Structure and Dynamics

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The effect of the conformational freedom of the ethanolamine tail of gramicidin A on the energy profile for the tfansfer of Na+, computed in the presence of water, shows an appreciable lowering of the minimum at 10.5 A, and a splitting of the entrance barrier. The deep energy region at the channel mouth remains, however, the deepest one and contains a site of sfrong interaction of the ion with the Trp 11 carbonyl, at about 12 A from the center. Gramicidin A Energy profire Ethanolamine end Water Na+ Theoretical computation

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Energy profiles in the gramicidin A channel

Abstract: Gramicidin A (GA) is a linear pentadecapeptide made of alternating D and L residues, in which the N-and C-terminals are blocked by a formyl group (head) and an ethanolamine end (tail), respectively (Sarges & Witkop, 1964):

Cited by 50 publications

References 57 publications

Photogating of ionic currents across a lipid bilayer.

Photogating of ionic currents across a lipid bilayer.

The Use of Physical Methods in Determining Gramicidin Channel Structure and Function

Energy Profile of Cs⁺in Gramicidin A in the Presence of Water. Problem of the Ion Selectivity of the Channel

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Energy profiles in the gramicidin A channel

Abstract: Gramicidin A (GA) is a linear pentadecapeptide made of alternating D and L residues, in which the N-and C-terminals are blocked by a formyl group (head) and an ethanolamine end (tail), respectively (Sarges & Witkop, 1964):

Cited by 50 publications

References 57 publications

Photogating of ionic currents across a lipid bilayer.

Photogating of ionic currents across a lipid bilayer.

The Use of Physical Methods in Determining Gramicidin Channel Structure and Function

Energy Profile of Cs+in Gramicidin A in the Presence of Water. Problem of the Ion Selectivity of the Channel

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Product

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Energy Profile of Cs⁺in Gramicidin A in the Presence of Water. Problem of the Ion Selectivity of the Channel