Ion channel stabilization of synthetic alamethicin analogs by rings of inter-helix H-bonds
| Autor: | Gérard Molle, Gérard Spach, Hervé Duclohier, J.Y. Dugast |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Membrane potential
Alamethicin Chemistry Stereochemistry Hydrogen bond Kinetics Lipid Bilayers Molecular Sequence Data Biophysics Electric Conductivity Conductance Hydrogen Bonding Biophysical Phenomena Ion Channels Protein Structure Secondary Membrane Potentials chemistry.chemical_compound Helix Amino Acid Sequence Lipid bilayer Ion channel Research Article |
| Zdroj: | Biophysical journal. 70(4) |
| ISSN: | 0006-3495 |
| Popis: | Rings of inter-helix H-bonds due to Gln at position 7, a highly conserved residue in all pore-forming peptaibols, have been suggested to play an important role in the stabilization of alamethicin channels. In an attempt to test this hypothesis, experimental studies have been undertaken on four synthetic alamethicin non-Aib analogs (Alm-dUL) in which the Gln at position 7 (Q7) is substituted by Ala, Asn, or Ser (Q7A, Q7N, or Q7S). Voltage-dependent pore formation by these analogs in planar lipid bilayers is compared at the macroscopic and single-channel conductance levels. As anticipated, the Q7A substitution abolished all channel-forming activity. The voltage dependence of macroscopic current-voltage curves was conserved with the Q7N substitution but reduced in the Q7S analog. Normalized single-channel conductance ratios between substates follow the same pattern, with the Q7S analog yielding the highest unit conductances. Channel lifetimes were the most significantly modulated parameter with markedly faster kinetics when Gln or Asn was replaced by Ser. The effect of the Q7S substitution on channel lifetimes may be explained through a reduced stabilization of bundles by inter-helix H-bonds. |
| Databáze: | OpenAIRE |
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