Insight into the Mechanism of the Influenza A Proton Channel from a Structure in a Lipid Bilayer

Abstract

M2 Out of the Envelope: The M2 protein from influenza A virus forms an acid-activated tetrameric proton channel in the viral envelope and is essential for viral replication. Two manuscripts shed light on the functional mechanism of this channel. Sharma et al. (p. 509 ; see the Perspective by Fiorin et al. ) determined the structure of the conductance domain in a lipid bilayer and propose that a histidine and tryptophan from each monomer form a cluster that guides protons through the channel in a mechanism that involves forming and breaking hydrogen bonds between adjacent pairs of histidines. Hu et al. (p. 505 ; see the Perspective by Fiorin et al. ) focused on the structure and dynamics of the proton-selective histidine at high and low pH, proposing that proton conduction involves histidine deprotonation and reprotonation.