Stabilizing Effect of D-Alanine(2) in Gramicidin Channels
by Mattice, Gwendolyn L.; Koeppe II, R. Erdman; Providence, Lyndon L.; Andersen, Olaf S.
We have investigated the effects of replacing Gly(2) by D-Ala(2) in gramicidin A (gA) analogues that have either L-Val, L-Ala, or Gly as the formyl-N-terminal residue. Circular dichroism, two-dimensional nuclear magnetic resonance, and hybrid channel experiments all show that [Ala(1),D-Ala(2)]gA channels are structurally equivalent to the native [Val(1),Gly(2)]gA channels, being formyl-NH-to-formyl-NH dimers of single-stranded, right-handed beta(6.3) helices. Replacing the Val(1) of gA by Ala or Gly decreases the average channel duration, Replacing Gly(2) by D-Ala in [Val(1),Gly(2)]gA increases the average channel duration 4-fold and the single-channel conductance by similar to 15%; replacing Gly(2) with D-Ala in [Ala(1),Gly(2)]gA or [Gly(1),Gly(2)]gA leads in each case to a 10-fold increase in the average channel duration with only modest changes in the single-channel conductance, which depends on the identity of the position-one residue and the permeant ion. These results illustrate the importance of neighboring-residue side chain and backbone interactions for the modulation of channel properties.
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- 1520-4995; 0006-2960