How can the aromatic side-chains modulate the conductance of the gramicidin channel? A new approach using non-coded amino acids.
In order to elucidate the role of the aromatic side-chains in the mechanism of transduction of monovalent cations through the channel of linear gramicidin, two series of analogues containing non-coded aromatic amino acids were synthesized. In the first series, the four tryptophans were replaced by either four L-3-(8-quinolyl)alanyl or four L-3-(4-quinolyl)alanyl residues and single channel conductance measurements showed that these substitutions led to a strong lowering of the channel conductance, which is attributed to a modification of the orientation of the aromatic side-chains due to an increase of their hydrophobicity. In the second series, the analogues contained both tryptophyl and naphthylalanyl residues in various amounts and positions. The single channel conductance data indicated that the conductance was mainly governed by the number of polar residues (Trp) and not by their positions. The conformational consequences of these results are discussed together with their influence on the energy profile of the gramicidin channel.
Daumas
P
P
Laboratory of Polyphasic System Physiochemistry, CNRS, Paris, France.
Benamar
D
D
Heitz
F
F
Ranjalahy-Rasoloarijao
L
L
Mouden
R
R
Lazaro
R
R
Pullman
A
A
D000409:Alanine / Q000031:analogs & derivatives / Q000378:metabolism; D002414:Cations, Monovalent / Q000378:metabolism; D002942:Circular Dichroism; D006096:Gramicidin / Q000737:chemistry* / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry; D015398:Signal Transduction; D013057:Spectrum Analysis; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism
D002414:Cations, Monovalent; D007473:Ion Channels; D008051:Lipid Bilayers; D006096:Gramicidin; C059031:1-naphthylalanine; D014364:Tryptophan; D000409:Alanine