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

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.

Functional control of a 0.5 MDa TET aminopeptidase by a flexible loop revealed by MAS NMR

“…Unlike solution-state NMR, magic-angle spinning (MAS) NMR does not face inherent protein size limitations and allows to see, in principle, each atom. MAS NMR is a powerful technique for studying dynamics at atomic resolution, and has been applied to sedimented, crystalline, membrane and amyloid proteins (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). Most of the previous MAS NMR dynamics studies focused on proteins below 20-30 kDa, as the resonance overlap often encountered in larger proteins complicates analyses.…”

A Machine Learning Model to Classify Dynamic Processes in Liquid Water**

“…Also, since interchange processes are closely related to the H-bond network dynamics, it is likely to play a critical role in biological processes, like proton transfer. [28][29][30][31][32] So far, interchange processes have been found in water dimer adsorbed on metal surfaces. [15] Using ab initio molecular dynamics (AIMD) simulations, [33] Ranea et al [23] found that the interchange process can be used to explain the rapid diffusion behavior of water dimer on the Pd(111) surface.…”

“…The interchange process, which involves the quantum tunneling effect, [15,23,25–27] is essential for understanding water molecules’ dynamics. Also, since interchange processes are closely related to the H‐bond network dynamics, it is likely to play a critical role in biological processes, like proton transfer [28–32] . So far, interchange processes have been found in water dimer adsorbed on metal surfaces [15] .…”

Molecular interaction and partitioning in α-keratin using 1 H NMR spin-lattice ( T 1 ) relaxation times

“…The water molecules which interact with the protein can be further broken down to fast and slow relaxing regimes [25,26]. These two components relate to a relatively immobile 'bound' population and a more labile 'free' population [25,[27][28][29]. Both populations undergo some exchange [30].…”