Engineering the gramicidin channel

by Koeppe, R. E.; Andersen, O. S.

The chemical design or redesign of proteins with significant biological activity presents formidable challenges. Ion channels offer advantages for such design studies because one can examine the function of single molecular entities in real time. Gramicidin channels are attractive for study because of their known structure and exceptionally well-defined function. This article focuses on amino acid sequence changes that 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-dependent channel gating. The findings provide insight into the folding of integral membrane proteins, the importance of tryptophan residues at the membrane/water interface, and the mechanism of channel gating.

Journal
Annual Review of Biophysics and Biomolecular Structure
Volume
25
Year
1996
Start Page
231-258
URL
https://dx.doi.org/10.1146/annurev.bb.25.060196.001311
ISBN/ISSN
1056-8700
DOI
10.1146/annurev.bb.25.060196.001311