On the Helix Sense of Gramicidin-a Single Channels

by Koeppe, R. E.; Providence, L. L.; Greathouse, D. V.; Heitz, F.; Trudelle, Y.; Purdie, N.; Andersen, O. S.

In order to resolve whether gramicidin A channels are formed by right- or left-handed beta-helices, we synthesized an optically reversed (or mirror image) analogue of gramicidin A, called gramicidin A-, to test whether it forms channels that have the same handedness as channels formed by gramicidin M- (F. Heitz et al., Biophys. J. 40:87-89,1982). In gramicidin M- the four tryptophan residues have been replaced with phenylalanine, and the circular dichroism (CD) spectrum therefore reflects almost exclusively contributions from the polypeptide backbone. The CD spectrum of gramicidin M- in dimyristoylphosphatidylcholine vesicles is consistent with a left-handed helical backbone folding motif (F. Heitz et al., Biophys. Chem. 24:149-160, 1986), and the CD spectra of gramicidins A and A- are essentially mirror images of each other. Based on hybrid channel experiments, gramicidin A- and M-channels are structurally equivalent, while gramicidin A and A- channels are nonequivalent, being of opposite helix sense. Gramicidin A- channels are therefore left-handed, and natural gramicidin A channels in phospholipid bilayers are right-handed beta-6.3-helical dimers.

Journal
Proteins-Structure, Function, and Bioinformatics
Volume
12
Issue
1
Year
1992
Start Page
49-62
URL
https://dx.doi.org/10.1002/prot.340120107
ISBN/ISSN
1097-0134; 0887-3585
DOI
10.1002/prot.340120107