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Gramicidin-based Fluorescence Assay; for Determining Small Molecules Potential for Modifying Lipid Bilayer Properties
Published on: October 13, 2010
Gramicidin tryptophans mediate formamidinium-induced channel stabilization
1Department of Physiology, Brown University, Providence, Rhode Island 02912, USA.
Biophysical Journal
|June 1, 1995
Summary
Formamidinium ions stabilize gramicidin A channels, but this effect depends on tryptophan side chains. Replacing tryptophans with phenylalanines eliminates stabilization and associated electrical properties, indicating tryptophan
Area of Science:
- Biophysics
- Membrane protein stabilization
- Ion channel function
Background:
- Formamidinium ions stabilize gramicidin A channels in lipid bilayers.
- This stabilization effect is also observed in N-acetyl gramicidin channels.
- The precise mechanism of formamidinium-mediated stabilization is not fully understood.
Purpose of the Study:
- To investigate the role of tryptophan side chains in formamidinium-induced gramicidin A channel stabilization.
- To elucidate the molecular basis of formamidinium interactions with gramicidin A channels.
- To determine how tryptophan modifications affect channel electrophysiology and noise.
Main Methods:
- Electrophysiological measurements using gramicidin analogs with tryptophan-to-phenylalanine substitutions (gramicidin M-).
- Comparison of channel behavior in monoolein and monoolein ether lipid bilayers.
- Analysis of current-voltage relationships, channel lifetime, and open-channel noise.
Main Results:
- Formamidinium-induced stabilization was eliminated in gramicidin M- where all four tryptophans were replaced by phenylalanines.
- Tryptophan residues 9, 13, and 15 are crucial for stabilization; Trp-11 plays a minor role.
- Formamidinium-dependent current-voltage supralinearity and open-channel noise were absent in gramicidin M-.
Conclusions:
- Formamidinium-induced gramicidin A channel stabilization is mediated by tryptophan side chains.
- Specific tryptophan residues (9, 13, 15) cooperate to mediate this effect.
- Formamidinium interactions with tryptophans influence channel lifetime, electrical properties, and noise, likely via water or lipid headgroup interactions.
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