Ion channel stabilization of synthetic alamethicin analogs by rings of inter-helix H-bonds.

AUTOR(ES)

Molle, G

RESUMO

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.

Documentos Relacionados

• Influence of proline position upon the ion channel activity of alamethicin.
• Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly rectifying potassium channel
• Intrinsic rectification of ion flux in alamethicin channels: studies with an alamethicin dimer.
• Stabilization of phage T4 lysozyme by engineered disulfide bonds.
• α-Helical stabilization by side chain shielding of backbone hydrogen bonds