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

David D. Busath, Craig D. Thulin, Richard W. Hendershot, L. Revell Phillips, Peter Maughan, Chad D. Cole, Nathan C. Bingham, Sara Morrison, Lissa Baird, Reed J. Hendershot, Myriam Cotten, Timothy A. Cross

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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, 1M 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.

Original languageEnglish (US)
Pages (from-to)2830-2844
Number of pages15
JournalBiophysical Journal
Volume75
Issue number6
StatePublished - Dec 1998
Externally publishedYes

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Gramicidin
Halogenation
Monoglycerides
Lipids
Ether
Fatty Acids
indole
1,2-diphytanoylphosphatidylcholine

ASJC Scopus subject areas

  • Biophysics

Cite this

Busath, D. D., Thulin, C. D., Hendershot, R. W., Phillips, L. R., Maughan, P., Cole, C. D., ... Cross, T. A. (1998). Noncontact dipole effects on channel permeation. I. Experiments with (5F-indole)Trp13 gramicidin A channels. Biophysical Journal, 75(6), 2830-2844.

Noncontact dipole effects on channel permeation. I. Experiments with (5F-indole)Trp13 gramicidin A channels. / Busath, David D.; Thulin, Craig D.; Hendershot, Richard W.; Phillips, L. Revell; Maughan, Peter; Cole, Chad D.; Bingham, Nathan C.; Morrison, Sara; Baird, Lissa; Hendershot, Reed J.; Cotten, Myriam; Cross, Timothy A.

In: Biophysical Journal, Vol. 75, No. 6, 12.1998, p. 2830-2844.

Research output: Contribution to journalArticle

Busath, DD, Thulin, CD, Hendershot, RW, Phillips, LR, Maughan, P, Cole, CD, Bingham, NC, Morrison, S, Baird, L, Hendershot, RJ, Cotten, M & Cross, TA 1998, 'Noncontact dipole effects on channel permeation. I. Experiments with (5F-indole)Trp13 gramicidin A channels', Biophysical Journal, vol. 75, no. 6, pp. 2830-2844.
Busath DD, Thulin CD, Hendershot RW, Phillips LR, Maughan P, Cole CD et al. Noncontact dipole effects on channel permeation. I. Experiments with (5F-indole)Trp13 gramicidin A channels. Biophysical Journal. 1998 Dec;75(6):2830-2844.
Busath, David D. ; Thulin, Craig D. ; Hendershot, Richard W. ; Phillips, L. Revell ; Maughan, Peter ; Cole, Chad D. ; Bingham, Nathan C. ; Morrison, Sara ; Baird, Lissa ; Hendershot, Reed J. ; Cotten, Myriam ; Cross, Timothy A. / Noncontact dipole effects on channel permeation. I. Experiments with (5F-indole)Trp13 gramicidin A channels. In: Biophysical Journal. 1998 ; Vol. 75, No. 6. pp. 2830-2844.
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AU - Phillips, L. Revell

AU - Maughan, Peter

AU - Cole, Chad D.

AU - Bingham, Nathan C.

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AB - 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, 1M 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.

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