Mechanisms of Proton Conduction and Gating in Influenza M2 Proton Channels from Solid-State NMR

<jats:title>M2 Out of the Envelope</jats:title> <jats:p> 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. <jats:bold> Sharma <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="509" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1191750">509</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6003" page="456" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1197748"> Fiorin <jats:italic>et al.</jats:italic> </jats:related-article> </jats:bold> ) 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. <jats:bold> Hu <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="505" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1191714">505</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6003" page="456" related-article-type="in-this-issue" vol="330" xlink:href="10.1126/science.1197748"> Fiorin <jats:italic>et al.</jats:italic> </jats:related-article> </jats:bold> ) 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. </jats:p>