1-palmitoyl-2-oleoylglycero-3-phosphoglycerol and tetrabutylammonium

Water-filled hydrophobic cavities in channel proteins serve as gateways for transfer of ions across membranes, but their properties are largely unknown. We determined water distributions along the conduction pores in two tetrameric channels embedded in lipid bilayers using neutron diffraction: potassium channel KcsA and the transmembrane domain of M2 protein of influenza A virus. For the KcsA channel in the closed state, the distribution of water is peaked in the middle of the membrane, showing water in the central cavity adjacent to the selectivity filter. This water is displaced by the channel blocker tetrabutyl-ammonium. The amount of water associated with the channel was quantified, using neutron diffraction and solid state NMR. In contrast, the M2 proton channel shows a V-shaped water profile across the membrane, with a narrow constriction at the center, like the hourglass shape of its internal surface. These two types of water distribution are therefore very different in their connectivity to the bulk water. The water and protein profiles determined here provide important evidence concerning conformation and hydration of channels in membranes and the potential role of pore hydration in channel gating.

Topics: Bacterial Proteins; Cell Membrane; Escherichia coli; Gene Expression; Influenza A virus; Ion Channel Gating; Ion Transport; Lipid Bilayers; Models, Molecular; Phosphatidylcholines; Phosphatidylglycerols; Potassium; Potassium Channel Blockers; Potassium Channels; Protein Conformation; Protein Multimerization; Protons; Quaternary Ammonium Compounds; Recombinant Proteins; Streptomyces lividans; Viral Matrix Proteins; Water