Structural and dipolar properties of the voltage-dependent pore former alamethicin in octanol/dioxane

Schwarz, Gerhard; Savko, P.

doi:10.1016/s0006-3495(82)84510-4

Cited by 62 publications

(34 citation statements)

References 12 publications

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“…Upon application of a sufficiently large voltage these aggregates are converted into arrays of parallel helices, which form water-filled ion conducting channels. Large dipole moments of 60-75 D have been determined for alamethicin (Schwarz & Savko, 1982;Yantorno, Takashima & Mueller, 1982) and trichotoxin A40 (Schwarz, Savko & Jung, 1983). Elementary dipoles originate from the charge separation phenomenon at peptide bonds (Hol et al, 1978) and sum up to macrodipoles in case of rods of helical structure (Hol, Halie & Sander, 1981;Hol, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the insertion of helical polypeptides into lipid bilayers is mainly determined by the electric field within the membrane as well as by electrostatic interaction between the dipolar molecules themselves. Added to one side of the bilayer, helical rods Such a mechanism has been proposed for alamethicin , which exhibits a large intrinsic dipole moment (Schwarz & Savko, 1982;Yantorno et al, 1982). If polypeptides are added to both sides of a planar bilayer, the spontaneous establishment of larger aggregates of antiparallel oriented dimers seems to be energetically favored.…”

Section: Weakly Voltage-dependent Conductancementioning

confidence: 99%

“…This explains the similarities in channel forming properties of P5 and P10. It is worth mentioning that head-to-tail aggregation was also observed with alamethicin and trichotoxin in octanol (Schwarz & Savko, 1982;Schwarz et al, 1983). Chain lengths of the various helices were estimated in Table 5 using the following distances per amino acid (Bosch, 1984): 1.5 A (a-helix) and 2.0 A (310-helix).…”

Section: Unit Channel Conductancementioning

confidence: 99%

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Voltage-dependent channel formation by rods of helical polypeptides

et al. 1986

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The voltage-dependence of channel formation by alamethicin and it natural analogues can be described by a dipole flip-flop gating model, based on electric field-induced transbilayer orientational movements of single molecules. These field-induced changes in orientation result from the large permanent dipole moment of alamethicin, which adopts alpha-helical conformation in hydrophobic medium. It was, therefore, supposed that the only structural requirement for voltage-dependent formation of alamethicin-type channels might be a rigid lipophilic helical segment of minimum length. In order to test this hypothesis we synthesized a family of lipophilic polypeptides--Boc-(Ala-Aib-Ala-Aib-Ala)n-OMe, n = 1-4--which adopt alpha-helical conformation for n = 2-4 and studied their interaction with planar lipid bilayers. Surprisingly, despite their large difference in chain length, all four polypeptides showed quantitatively similar behavior. At low field strength of the membrane electric field these polypeptides induce a significant, almost voltage-independent increase of the bilayer conductivity. At high field strength, however, a strongly voltage-dependent conductance increase occurs similar to that observed with alamethicin. It results from the opening of a multitude of ion translocating channels within the membrane phase. The steady-state voltage-dependent conductance depends on the 8th-9th power of polypeptide concentration and involves the transfer of 4-5 formal elementary charges. From the power dependences on polypeptide concentration and applied voltage of the time constants in voltage-jump current-relaxation experiments, it is concluded that channels could be formed from preexisting dodecamer aggregates by the simultaneous reorientation of six formal elementary charges. Channels exhibit large conductance values of several nS, which become larger towards shorter polypeptide chain length. A mean channel diameter of 19 A is estimated corresponding roughly to the lumen diameter of a barrel comprised of 10 alpha-helical staves. Similar to experiments with the N-terminal Boc-derivative of alamethicin we did not observe the burst sequence of nonintegral conductance steps typical of natural (N-terminal Ac-Aib)-alamethicin. Saturation in current/voltage curves as well as current inactivation in voltage-jump current-relaxation experiments are found. This may be understood by assuming that channels are generated as dodecamers but, while reaching the steady state, reduce their size to that of an octamer or nonamer. We conclude that the overall behavior of these synthetic polypeptides is very similar to that of alamethicin.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionmentioning

confidence: 99%

Section: Weakly Voltage-dependent Conductancementioning

confidence: 99%

Section: Unit Channel Conductancementioning

confidence: 99%

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Voltage-dependent channel formation by rods of helical polypeptides

et al. 1986

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“…5 It has been suggested that the alamethicin monomer is about 3.5 nm in length and carries a dipole moment of approximately 75 D units, which is responsible for the voltage- dependent conductance. 6,7 We can conclude that the QDs, having a permanent dipole moment 8 similar to alamethicin, are influenced by an external electric field, which creates a torque on the QD dipole, forcing insertion into the lipid membrane ͓Fig. 1͑a͔͒.…”

Section: ͑23°c͒mentioning

confidence: 99%

Current bursts in lipid bilayers initiated by colloidal quantum dots

Ramachandran

Kumar

Blick

et al. 2005

Applied Physics Letters

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Inorganic semiconductor nanocrystals, also called quantum dots, have recently attracted considerable interest as fluorescent labels. We report that CdSe QDs initiate current bursts in lipid bilayer membranes upon application of a bias voltage. The current bursts observed resemble those produced by the peptaibol class of antibiotics such as alamethicin and trichorzins. The current fluctuations are dependent on the bias voltage and on the concentration of the quantum dots applied to the membrane. Our data suggest that quantum dots with dipole moments similar to alamethicin are influenced by an external electric field, which creates a torque resulting in the insertion into the lipid membrane. We predict that at least three quantum dots are required to form a pore due to aggregation that leads to a macroscopic conductance.

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“…In the case of Alm this behaviour is best explained in terms of re-orientation of the helix dipole (Hole et al 1978;Schwarz and Savko 1982) in the imposed electric field (Boheim et al 1983;Mathew and Balaram 1983;Sansom 1991). The negatively charged residue near the C-terminus (El8) is believed to anchor the C-terminus at the bilayer-water interface, and thus only when a cis positive potential is applied is the helix able to reorient itself in the bilayer, by repulsion of the formal positive charge (+ 1/2) at the N-terminus.…”

Section: ) Voltage Activationmentioning

confidence: 99%

The properties of ion channels formed by zervamicins

et al. 1992

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The zervamicins (Zrv) are a family of 16 residue peptaibol channel formers, related to the 20 residue peptaibol alamethicin (Alm), but containing a higher proportion of polar sidechains. Zrv-IIB forms multi-level channels in planar lipid (diphytanoyl phosphatidylcholine) bilayers in response to cis positive voltages. Analysis of the voltage and concentration dependence of macroscopic conductances induced by Zrv-IIB suggests that, on average, channels contain ca. 13 peptide monomers. Analysis of single channel conductance levels suggests a similar value. The pattern of successive conductance levels is consistent with a modified helix bundle model in which the higher order bundle are distorted within the plane of the bilayer towards a "torpedo" shaped cross-section. The kinetics of intra-burst switching between adjacent conductance levels are shown to be approximately an order of magnitude faster for Zrv-IIB than for Alm. The channel forming properties of the related naturally occurring peptaibols, Zrv-Leu and Zrv-IC, have also been demonstrated, as have those of the synthetic apolar analogue Zrv-Al-16. The experimental studies on channel formation are combined with the known crystallographic structures of Zrv-Al-16 and Zrv-Leu to develop a molecular model of Zrv-IIB channels.

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Structural and dipolar properties of the voltage-dependent pore former alamethicin in octanol/dioxane

Cited by 62 publications

References 12 publications

Voltage-dependent channel formation by rods of helical polypeptides

Voltage-dependent channel formation by rods of helical polypeptides

Current bursts in lipid bilayers initiated by colloidal quantum dots

The properties of ion channels formed by zervamicins

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