The Architecture of a Water-Selective Pore in the Lipid Bilayer Visualized by Electron Crystallography in Vitreous Ice

Summary

The water-selective pathway through aquaporin 1 (AQP1) membrane channel has been visualized by fitting an atomic model to a 3.7 Å resolution three-dimensional density map. This map was determined by analysing images and electron diffraction patterns of lipid-reconstituted two-dimensional crystals of AQP1 preserved in vitrified buffer in the absence of any additive. The aqueous pathway in a monomer is characterized by a size-selective, ∼4.0±0.5 Å wide pore that spans a length of ∼18 Å and bends by ∼25° as it traverses the bilayer. This narrow pore is connected by wide, funnel-shaped openings at the extracellular and cytoplasmic faces, and is outlined mostly by hydrophobic residues interspersed with short stretches of polar amino acids, which results in relatively inert pathway conducive to diffusion-limited water flow. Although not visible at the current resolution, the 3D structure suggests putative binding sites for water molecules in the size-selective pore.