ENGINEERING THE GRAMICIDIN CHANNEL

The chemical design or redesign of proteins with significant biologica l activity presents formidable challenges. Ion channels offer advantag es for such design studies because one can examine the function of sin gle molecular entities in real time. Gramicidin channels are attractiv e for study because of their known structure and exceptionally well-de fined function. This article focuses on amino acid sequence changes th at redesign the structure or function of gramicidin channels. New, and functional, folded states have been achieved. In some cases, a single amino acid sequence can give rise to several (up to three) functional conformations. Single amino acid substitutions confer voltage-depende nt channel gating. The findings provide insight into the folding of in tegral membrane proteins, the importance of tryptophan residues at the membrane/water interface, and the mechanism of channel gating.