Lipid-protein interactions in double-layered two-dimensional AQPO crystals

Lens- specific aquaporin-O ( AQPO) functions as a specific water pore and forms the thin junctions between fibre cells. Here we describe a 1.9 angstrom resolution structure of junctional AQPO, determined by electron crystallography of double-layered two- dimensional crystals. Comparison of junctional and non- junctional AQPO structures shows that junction formation depends on a conformational switch in an extracellular loop, which may result from cleavage of the cytoplasmic amino and carboxy termini. In the centre of the water pathway, the closed pore in junctional AQPO retains only three water molecules, which are too widely spaced to form hydrogen bonds with each other. Packing interactions between AQPO tetramers in the crystalline array are mediated by lipid molecules, which assume preferred conformations. We were therefore able to build an atomic model for the lipid bilayer surrounding the AQPO tetramers, and we describe lipid - protein interactions.