Water orientation and dynamics in the closed and open influenza B virus M2 proton channels

The influenza B M2 protein forms a water-filled tetrameric channel to conduct protons across the lipid membrane. To understand how channel water mediates proton transport, we have investigated the water orientation and dynamics using solid-state NMR spectroscopy and molecular dynamics (MD) simulations. C-13-detected water H-1 NMR relaxation times indicate that water has faster rotational motion in the low-pH open channel than in the high-pH closed channel. Despite this faster dynamics, the open-channel water shows higher orientational order, as manifested by larger motionally-averaged H-1 chemical shift anisotropies. MD simulations indicate that this order is induced by the cationic proton-selective histidine at low pH. Furthermore, the water network has fewer hydrogen-bonding bottlenecks in the open state than in the closed state. Thus, faster dynamics and higher orientational order of water molecules in the open channel establish the water network structure that is necessary for proton hopping. To understand how water in the channel made of the influenza B M2 protein mediates proton transport across the lipid membrane, Gelenter et al. investigate the water orientation and dynamics. This study suggests that faster dynamics and higher orientational order of water molecules in the open channel compared to the closed one establish the water network structure that is necessary for proton hopping.