Aquaporins: Structure
Aquaporins are made up of six transmembrane α-helices arranged in a right-handed bundle, with the amino and the carboxyl termini located on the cytoplasmic surface of the membrane. The amino and carboxyl halves of the sequence show similarity to each other, in what appears to be a tandem repeat. Some researches believe that this results from an early evolution event which saw the duplication of the half sized gene. There are also five interhelical loop regions (A – E) that form the extracellular and cytoplasmic vestibules. Loops B and E are hydrophobic loops which contain the highly, although not completely conserved Asn-Pro-Ala (NPA) motif, which overlap the middle of the lipid bilayer of the membrane forming a 3-D 'hourglass' structure where the water flows through. This overlap forms one of the two well-known channel constriction sites in the peptide, the NPA motif and a second and usually narrower constriction known as 'selectivity filter' or ar/R selectivity filter.


Aquaporins form tetramers in the cell membrane, and facilitate the transport of water and, in some cases, other small uncharged solutes, such as glycerol, CO2, ammonia and urea across the membrane depending on the size of the pore. The different aquaporins contain differences in their peptide sequence which allows for the size of the pore in the protein to differ between aquaporins. The resultant size of the pore directly affects what molecules are able to pass through the pore, with small pore sizes only allowing small molecules like water to pass through the pore. However, the water pores are completely impermeable to charged species, such as protons, a property critical for the conservation of membrane's electrochemical potential.



NPA motif

Using computer simulations it has been suggested that the orientation of the water molecules moving through the channel assures that only water passes between cells, due to the formation of a single line of water molecules. The water molecules move through the narrow channel by orienting themselves in the local electrical field formed by the atoms of the channel wall. Upon entering, the water molecules face with their oxygen atom down the channel. Midstream, they reverse orientation, facing with the oxygen atom up. This rotation of the water molecules in the pore is carried out by the interaction of hydrogen bonds between the oxygen of the water molecule and the asparagines in the two NPA motifs. While passing through the channel, the single-file chain of water molecules streams through, always entering face down and leaving face up. The strictly opposite orientations of the water molecules keep them from conducting protons (or rather oxonium ions, H3O+), while still permitting a fast flux of water molecules .

ar/R selectivity filter

The ar/R (aromatic/arginine) selectivity filter is a tetrad that is formed by two residues from helices 2 (H2) and 5 (H5) and two residues form loop E (LE1 and LE2), found on either side of the NPA motif. The ar/R region is usually found towards the extracellular vestibule, approximately 8Å above the NPA motif and is often the narrowest part of the pore. The narrow pore acts to weaken the hydrogen bonds between the water molecules allowing the water to interact with the positively charged arginine, which also acts as a proton filter for the pore.








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