Conduction processes of the gramicidin channel

Abstract

The significance of the gramicidin channel, its structural elements, and the importance of the peptide libration mechanism are reviewed. Elemental ionic processes of the single-channel currents are considered, which indicate the possibility of two-and three-site models. Data are presented which demonstrate the absence of interactions required for the three-site model, and the resulting freeenergy profile for the two-site model is given for the most probable conducting state. The need to extend analyses to include an understanding of multiple conformational states is outlined, and results from approximate conformational energy calculations are presented showing that there are numerous low-energy conformations for the side chains of gramicidin. Specifically the interactions between L.Trp9 and L.Trpl=, side chains and between D-Leud. . .D-LeUjo are analyzed to show the existence of several energy minima separated by appreciable barriers. These findings provide the basis for understanding facilitated entry of the second ion into the channel and the occurrence of lipid-dependent dispersion of conductance states. Finally perspectives of the molecular mechanism of anesthetics are discussed relevant to the gramicidin channel mean lifetime and single-channel currents.

Circular Dichroism Studies of Tryptophan Residues in Gramicidin

“…Raman spectroscopy has indicated a narrow range of Trp X2 angles in the channel form of gramicidin [12]. This corroborates energy calculations which have indicated large barriers for side chain rotation [13]. Indeed the near-UV CD pattern we observe persists at least to 70 o C which is a further indication of rather rigid side chain conformation(s).…”

The different influences of ether and ester phospholipids on the conformation of gramicidin A. A molecular modelling study

“…Fu~hermore, the importance of the side-chain rotational state on the mean life-time of the channel and hence the transporting properties is also apparent from a previous theoretical study on gramicidin analogues that are not surrounded by other molecules [4,7]. When considering lipid-gramicidin interactions, the eonformational distribution of the Trp-15 side-chain is particularly of interest.…”

“…It can be imagined that by adopting a different phospholipid chain packing, the structure of embedded proteins may very well be modified. For instance, it has been argued, based on theoretical investigations, that the channel-forming polypeptide gramicidin A can be influenced by the lipid environment via conformational changes in the peptide residues, resulting in different conductivities through the channel [4].…”

“…When considering lipid-gramicidin interactions, the eonformational distribution of the Trp-15 side-chain is particularly of interest. This residue is situated in the vicinity of the lipid/water interface and, moreover, the molecular structure of the channel entrance might easily be influenced by a change in the rotameric state of this side-chain [4].…”

Location of monovalent cation binding sites in the gramicidin channel.

“…Although there is yet much to be completed for a thorough understanding of the mechanism of channel transport as exemplified by the gramicidin channel-such as the facilitated on rate for the second ion (26) and the dispersion of single-channel currents (unpublished data) that have been proposed to arise from changes in side-chain rotameric states altering the energetics of libration (38) and such as the rate constant for jumping between sites during single occupancy, which has been estimated in the case ofTl by means ofdielectric relaxation studies (39)-what is now defined for the first time is the location of two binding sites within a transmembrane channel and an estimate of the repulsion attending double occupancy.…”