IMPORTANCE OF TRYPTOPHAN DIPOLES FOR PROTEIN FUNCTION - 5-FLUORINATION OF TRYPTOPHANS IN GRAMICIDIN-A CHANNELS

In integral membrane proteins the amphipathic aromatic amino acid resi dues tryptophan and tyrosine tend to be localized at membrane/solution interface. The interfacial location of these residues is likely to be significant for membrane protein structure and function. Trp and Tyr have complex chemical characteristics, however, and it is difficult to deduce how these side chains determine protein structure and function . Specifically, Trp and Tyr not only are amphipathic but also dipolar, and electrostatic interactions that involve the side chain dipoles co uld be important for function. We evaluate the importance of the Trp d ipole moment for ion channel function by replacing Trp residues in gra micidin A by the more polar 5-F-Trp and monitoring the ensuing changes in the conductance of membrane-spanning gramicidin channels. Trp-->5- F-Trp substitutions increase the conductance of the sequence-substitut ed channels, and we conclude that Trp side chains increase ion permeab ility through electrostatic interactions with the permeant cations.