The M2 protein of influenza A is a pH-activated, homotetrameric proton channel whose function is necessary for viral replication. The smallest construct that retains function has 100 total residues. Because of its small size, the M2 channel has been studied as a model system for the transport of protons across a membrane. Protons are shuttled across water wires that start at the N-terminus of the channel, pass through gating His37 residues, then move protons to the C-terminus of the channel. Crystal structures to a resolution of 1.1 � were determined for the AM2 proton channel transmembrane domain under high and low pH conditions in the lipidic cubic phase. Variations in the water network leading from the N-terminal half of the pore to residue His37 were observed with pH. Room temperature data collection was used to determine if and how the observed water networks were affected by the low temperature conditions of cryocrystallography. Molecular dynamics simulations were used to predict the positions of the water dipoles and the electrostatic potential of the channel at high and low pH.

High-resolution crystal structures of the influenza A M2 proton channel in the lipidic cubic phase: Insights into water networks at high and low pH

248th National Meeting (2014)

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