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September 2001
Vol. 4, No. 9, p 17.
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Crossing the channel

Voltage-gated ion channels are important to physiological functions such as nerve and muscle stimulation. A detailed understanding of channel gating has been impeded, however, by the difficulty of producing sufficient amounts of the proteins involved and the challenges of performing structural studies under physiologically relevant conditions.

figure
From dimer to dimmer. Dimerization of the modified gramicidin peptides (left) allows the excitation energy to undergo fluorescence resonance energy transfer (FRET) through the membrane. When the dimer is broken, this energy transfer cannot occur. (Adapted from Lougheed, T.; et al. Bioconj. Chem. 2001,12, 594–602.)
Andrew Woolley and colleagues at the University of Toronto use ion channels formed by the peptide gramicidin as a model system to develop a combined optical and electrical detection system that will provide new information on the structure and dynamics of ion-channel gating (Bioconj. Chem. 2001, 12, 594–602).

Gramicidin is a bacterial cytolytic transport peptide. Gramicidin readily incorporates into lipid bilayers as a β-helix such that channel formation occurs by an association of two gramicidin monomers and provides a pore that transverses the membrane. The channel permits the transmembrane flux of small monovalent cations, and channel closing is believed to be due to dissociation of the dimer into monomers.

Transmembrane ion-current measurements monitor changes that correspond to gramicidin dimerization. Woolleydescribed the synthesis and characterization of two pairs of fluorescently labeled gramicidin derivatives that are suitable for combined optical and electrical single-molecule experiments to monitor ion-channel formation. The peptide was derivatized at the membrane–solution interface with fluorescent dyes that can undergo fluorescence resonance energy transfer such that dimerization and ion-channel gating can be monitored. The technology should prove useful for efforts to decipher the conductance mechanism of gramicidin and other ion channels of medicinal importance under physiologically relevant conditions.

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