A conformational rearrangement in gramicidin A: From a double-stranded left-handed to a single-stranded right-handed helix

Zhang, Zhenlu; Pascal, Steven M.; Cross, Timothy A.

doi:10.1021/bi00152a019

Cited by 45 publications

(61 citation statements)

References 47 publications

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“…This model implies the existence of an intermediate between the double-stranded helix and single-stranded helical dimmer. In general, the present mechanism is more consistent with the flip-flop model, 26,27 since the ''zipper'' model involves several sequential steps and implies the existence of a series of intermediates. 24,25,29 The conformational change of gramicidin A in lipid vesicles is an extremely slow process compared to the usual water-soluble proteins, and this is reflected in the low values of the two rate constants between 10 À1 and 10 À3 per minute.…”

Section: à2supporting

confidence: 79%

“…In the second model, referred to as the ''flip-flop'' mechanism, the intertwined chains twist to dissociate, and the peptide planes reorient and flip to produce a structure with the opposite helical handedness. 26,27 However, the detailed mechanism underlying this structural conversion under the effect of temperature and lipid has not been fully studied.…”

Section: Introductionmentioning

confidence: 99%

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The effect of temperature and lipid on the conformational transition of gramicidin A in lipid vesicles

Lin¹,

Huang²,

Wei³

et al. 2005

Biopolymers

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The present study investigated the effect of temperature and lipid/peptide molar ratio on the conformational changes of the membrane peptide gramicidin A from a double-stranded helix to a single-stranded helical dimmer in 1,2-dimyristoyl-glycerol-3-phosphochloine (DMPC) vesicles. Tryptophan fluorescence spectroscopy results suggested that the conformational transition fitted a three-state (two-step) "folding" model. Rate constants, k(1) and k(2), were determined for each of the two steps. Since k(1) and k(2) increased with an increase in temperature, we hypothesized that the process corresponded to the breakage and formation of the backbone hydrogen bonds. The k(1) was from 10 to 45 folds faster than k(2), except for lipid/peptide molar ratios above 89.21, where k(2) increased rapidly. At molar ratios below 89.21, k(2) was insensitive to changes in lipid concentration. To account for this phenomenon, we proposed that while the driving interaction at high molar ratios is between the indole rings of the tryptophan residues and the lipid head groups, at low molar ratios there may be an intermolecular interaction between the tryptophan residues that causes gramicidin A to form an organized aggregated network. This aggregated network, caused by the tryptophan-tryptophan interaction, may be the main effect responsible for the slow down of the conformation change.

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Section: à2supporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

The effect of temperature and lipid on the conformational transition of gramicidin A in lipid vesicles

Lin¹,

Huang²,

Wei³

et al. 2005

Biopolymers

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“…While these samples are a mixture of gramicidin and lipid, the gramicidin is probably in a nonchannel conformation (Zhang et al, 1992 used for the predictions. Secondly, the chemical environment for Val, and Gly, is unusual.…”

Section: Resultsmentioning

confidence: 99%

Orientational constraints as three‐dimensional structural constraints from chemical shift anisotropy: The polypeptide backbone of gramicidin A in a lipid bilayer

Mai¹,

Hu²,

Wang³

et al. 1993

Protein Science

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Chemical shifts observed from samples that are uniformly aligned with respect to the magnetic field can be used as very high-resolution structural constraints. This constraint takes the form of an orientational constraint rather than the more familiar distance constraint. The accuracy of these constraints is dependent upon the quality of the tensor characterization. Both tensor element magnitudes and tensor orientations with respect to the molecular frame need to be considered. Here these constraints have been used to evaluate models for the channel conformation of gramicidin A. Of the three models used, the one experimentally derived model of gramicidin in sodium dodecyl sulfate micelles fits the data least well.

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“…The overall result in the present study is that the activation energy for the rate-limiting step is reduced substantially by the presence of water. There are many important questions that remain about this mechanism (it is still very much a hypothesis), but this stepwise unscrewing of the dimer has gained considerable experimental support (21,22,25) as the mechanism occurring in a lipid environment where the double-stranded structure unwinds to the single-stranded channel state. Here, the data provide additional support for this mechanism of conformer interconversion in an organic solvent system.…”

Section: Fig 2 (A)mentioning

confidence: 99%

Water: Foldase activity in catalyzing polypeptide conformational rearrangements

Cross

1999

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

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Polypeptide conformer interconversion in a low dielectric environment is shown to be highly dependent on water concentration. Water increases this rate by 10 3 , apparently by catalyzing hydrogen bond exchange, and thereby presenting functional properties analogous to that of a foldase. This catalytic effect is demonstrated on the interconversion of a parallel gramicidin dimer into an antiparallel dimer. A Hill coefficient of 6.5 is observed, illustrating the highly cooperative nature of the process. Protein folding in nonpolar environs, such as the hydrophobic core of a protein or the hydrophobic domain of a lipid bilayer, may be contingent on and rate-limited by the scarcity of water.

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A conformational rearrangement in gramicidin A: From a double-stranded left-handed to a single-stranded right-handed helix

Cited by 45 publications

References 47 publications

The effect of temperature and lipid on the conformational transition of gramicidin A in lipid vesicles

The effect of temperature and lipid on the conformational transition of gramicidin A in lipid vesicles

Orientational constraints as three‐dimensional structural constraints from chemical shift anisotropy: The polypeptide backbone of gramicidin A in a lipid bilayer

Water: Foldase activity in catalyzing polypeptide conformational rearrangements

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