Ion channels formed by chemical analogs of gramicidin A.
Channel-forming peptides such as gramicidin A offer the opportunity to study the relationship between chemical structure and transport properties of an ion channel. This article summarizes a number of recent experiments with chemical analogs and derivatives of gramicidin A using artificial lipid bilayer membranes. The introduction of negative charges near the channel mouth leads to an increase in the cation transport rate. Hybrid channels consisting of a neutral and a negatively charged or of a positively and a negatively charged half-channel may be formed. The current-voltage characteristic of these hybrid channels exhibits a pronounced asymmetry. Experiments with charged derivatives of gramicidin A have been used in order to distinguish between different structural models of the dimeric channel; these studies strongly support Urry's model of a single-stranded, head-to-head associated helical dimer. In a further set of experiments gramicidin analogs with modified amino acid sequence were studied. It was found that a single substitution (tryptophan replaced by phenylalanine) leads to marked changes in the conductance of the channel. Analogs with a simplified amino acid sequence such as (L-Trp-D-Leu)7-L-Trp or L-Trp-Gly-(L-Trp-D-Leu)6-L-Trp are able to form cation permeable channels with similar properties as gramicidin A.
D004553:Electric Conductivity; D006096:Gramicidin; D007473:Ion Channels / Q000378:metabolism / Q000648:ultrastructure*; D007526:Isoelectric Point; D007700:Kinetics; D008567:Membranes, Artificial; D008970:Molecular Weight; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D007473:Ion Channels; D008567:Membranes, Artificial; D006096:Gramicidin