Interfacial water screens the protein-induced transmembrane voltage

Transmembrane proteins are crucial in cellular traffic, signal transduction, and energy storage in a form of transmembrane voltage. These proteins are stabilized by hydrophobic and hydrophilic interactions, in which cytoplasmic and exoplasmic water plays a special role. Water structural ordering generates the dipole potential that typically overcompensates for an intrinsic membrane-protein potential gradient, and thus it modifies and sustains an overall cellular electrostatics. Although the transmembrane voltage has been extensively studied, the dipole potential has attracted very little attention. Here, by using molecular dynamics, we examined water electrostatic response to the transmembrane charge, field, and potential asymmetry introduced by the presence of four integral membrane proteins: typical of inner (α-helix) and outer membrane (β-barrel). In all cases, the protein presence introduces electrostatic directionality in the transmembrane dipole field and voltage. In particular, water generates a deep potential sink if strongly polar residues are densely packed on one side of bilayer, as frequently occurs in a selectivity filter of the K(+) channel. We also found that protein secondary structure is less important than the polar residue distribution along the protein channel. Our findings are relevant for understanding the driving force behind biomembrane conductivity: the ability of biological water to electrostatically screen the transmembrane voltage.