Wet Holes in the Membrane

09 May 2007 // protein

They say we are made up of 70% water. As our cells are wrapped in a membrane that keeps water out, we might as well be walking bags of water. That is, except for little holes in the membranes that lets water and only water pass through. These are the Aquaporin channels, the discovery of which, won Peter Agre the 2003 Nobel Prize.

The architecture of Aquaporin is exquisite – it let's in neutral water molecules, but keeps out charged protons and ions. Water flows freely into the cell without altering the charged polarity of the cell. How is that done?

Klaus Schulten and Emad Tajkhorsh, of UIUC, carried out an exhaustive simulation of water molecules flowing through aquaporin. From these simulations, we can see (below) in exquisite molecular detail, just how water molecules flow through the aquaporin channels:

The key to keep out ions are the two asparigines in the middle of the channel (displayed in stick). The top asparigine is positioned such that the water molecules in the top half of the channel form a single file of hydrogen-bonded water molecules with the hydrogens (white) of the water molecules pointing up.

The lower asparagine forces the hydrogens of the water molecules in the lower half of the channel to point down. Watch how the water molecules flip orientation in the middle of the channel. The yellow molecule is a water molecule, so marked in order for you to follow it's progress through the channel.

The opposing orientation of the upper and lower lines of water molecules result in opposing electrostatic dipole. An ion can only make it it to the middle before being forced back by the opposing electric dipole of the other half of the channel.

The animation above leaves a lot of detail out. To see in full detail, the complexity of modeling a channel in a protein in atomic detail, have a look at the animation of the simulation produced by Bert de Groot, & Helmut Grubmüller:

The Aquaporins are blue, the lipid in the protein are green (for the lipid) and yellow (for the polar heads).

Don't forget to thank your Aquaporins the next time you suck down a bottle of Gatorade as you don't suffer from death by electrolyte poisoing.