Studies of structural changes in the M2 proton channel of influenza A virus by tryptophan fluorescence

Abstract

Studies of tryptophan fluorescence of purified influenza A virus M2 protein have identified two pH-dependent structural changes. (1) An increase in fluorescence on reduction of pH from 8 to 6 that involves tryptophan 15 within the N-terminal domain of the protein and may be associated with proton activation of the channel. (2) Quenching of the fluorescence of tryptophan 41 within the transmembrane domain of the channel by histidine 37 below pH 6 which is specifically reversed by drugs that block the M2 channel. The pH dependence of the latter effect, which monitors changes in the protonation of histidine 37, corresponds to that of proton current through the channel and provides evidence for the involvement of histidine 37 in proton permeation.