ELECTROSTATIC EFFECTS ON ION SELECTIVITY AND RECTIFICATION IN DESIGNED ION-CHANNEL PEPTIDES

To help determine how amino acid sequence can influence ionic conducti on properties in alpha-helical structures, we have synthesized and stu died three closely related, channel-forming peptides. The sequences ar e based on a 21-residue amphiphilic Leu-Ser-Ser-Leu-Leu-Ser-Leu heptad repeat motif and differ in having either neutral, negatively, or posi tively charged N-termini. The channels formed by the neutral peptide a re modestly cation selective and exhibit asymmetric current-voltage cu rves arising from the partial charges at the ends of the alpha-helix. Addition of a negatively charged Glu residue converted the channel to a completely cation-selective structure and essentially eliminated its rectification. Addition of a positively charged Arg residue near the N-terminus of the peptide reduced this channel's cation selectivity an d increased the extent of rectification, These effects on channel ioni c conductance can be explained by a theoretical electrostatic model an d provide insights into the workings of more complex channel proteins.