Abstract
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. 13C-detected water 1H 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 1H 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.
Highlights
The influenza B M2 protein forms a water-filled tetrameric channel to conduct protons across the lipid membrane
When a protein channel contains more than a single file of water molecules and when proton conduction is predominantly unidirectional, both water dynamics and water–water hydrogen bonding are expected to affect proton transport[10]
The closed and open states are accessible by controlling the pH of the membrane samples to pH 7.5 (“high pH”) and pH 4.5 (“low pH”), ARTICLE
Summary
The influenza B M2 protein forms a water-filled tetrameric channel to conduct protons across the lipid membrane. The interplay among water dynamics, water–water hydrogen bonding, and water orientation for proton transport is not yet well understood This is partly due to the experimental challenges of determining atomic-resolution structures of membrane protein channels. M2 transports protons using a mixed hydrogen-bonded chain between water and histidine This detailed information about the histidine structure and dynamics in the influenza A M2 (AM2) protein was obtained from extensive solid-state NMR and crystallographic data[17,18,22,23,24]. Solid-state NMR data show that water in the low-pH BM2 channel exhibits faster reorientations as well as higher orientational order compared to the high-pH channel This unexpected result suggests that water undergoes rapid small-amplitude reorientations to mediate proton conduction. MD simulations give consistent findings about the relationship between water orientation and dynamics, and indicate that this relationship is controlled by the proton-selective histidine residue
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