Single-channel studies on linear gramicidins with altered amino acid sequences. A comparison of phenylalanine, tryptophane, and tyrosine substitutions at positions 1 and 11.
The relation between chemical structure and permeability characteristics of transmembrane channels has been investigated with the linear gramicidins (A, B, and C), where the amino acid at position 1 was chemically replaced by phenylalanine, tryptophane or tyrosine. The purity of most of the compounds was estimated to be greater than 99.99%. The modifications resulted in a wide range of conductance changes in NaCl solutions: sixfold from tryptophane gramicidin A to tyrosine gramicidin B. The conductance changes induced by a given amino acid substitution at position 1 are not the same as at position 11. The only important change in the Na+ affinity was observed when the first amino acid was tyrosine. No major conformational changes of the polypeptide backbone structure could be detected on the basis of experiments with mixtures of different analogues and valine gramicidin A (except possibly with tyrosine at position 1), as all the compounds investigated could form hybrid channels with valine gramicidin A. The side chains are not in direct contact with the permeating ions. The results were therefore interpreted in terms of modifications of the energy profile for ion movement through the channel, possibly due to an electrostatic interaction between the dipoles of the side chains and ions in the channel.
D000595:Amino Acid Sequence; D000818:Animals; D006096:Gramicidin; D007473:Ion Channels / Q000502:physiology*; D008433:Mathematics; D008954:Models, Biological; D008958:Models, Molecular; D010649:Phenylalanine; D013329:Structure-Activity Relationship; D014364:Tryptophan; D014443:Tyrosine
D007473:Ion Channels; D006096:Gramicidin; D014443:Tyrosine; D010649:Phenylalanine; D014364:Tryptophan