Water in biological pores-1 Aquaporin water channel

Membrane proteins Cells are surrounded by biological membranes that separate the cell’s interior from the outside world. These lipid bilayers are vital for the structural integrity of cells, and the proteins embedded in the lipid bilayer are responsible for: sensing the outside world the controlled exchange of substances between the cell and its environment maintaining electrochemical gradients that provide the energy for many physiological processes

Peter Agre Peter Agre received the 2003 Nobel Prize in Chemistry for his discovery of aquaporins He said “I am an hematologist, but sometimes in science what we find is not what we were looking for.” After the liquid bilayer was discovered in the 1920s, it was assumed that water permeability could be explained by simple diffusion through membranes But in certain tissues (renal tubule, red cells, secretory glands), the flow is much larger than the one could be explained by simple diffusion

Current view water may both diffuse through membranes and flow through aquaporins Aquaporins have large capacity and large selectivity for water the movement of water through aquaporins is driven by osmotic gradients

Peter Agre’s observations Red cells dropped into seawater will shrink because water leaves the cells; if dropped into fresh water they swell and explode because water enters the cell

Aquaporins (AQPs) The members of the aquaporin (AQP) family form transmembrane pores that are either exclusive permeable for water (aquaporins) or are also permeable for other small neutral solutes such as glycerol (aquaglyceroporins).

how aquaporin works there is a narrow pathway for water, the smallest biological molecule Surrounding residues (Arg and His) provide positive charges that repel protons Cys is the site for Hg++ inhibition

Impermeability for protons note orientation of water molecules in the top region, reorientation in the middle, opposite orientation at the bottom

how aquaporin works water transits the pore in single file

details of the pore the narrowest part of the pore has a diameter of 2.6 Å fixed charge on adjacent Arg repeals protons water in single file may form H-bonds with each other in the center of the pore one water molecule can form H-bonds to residues basically water moves without resistance

inhibition of proton transfer proton transfer in proteins occurs through a “proton wire”, i.e., a single file of water molecules with proper orientations since aquaporin has a single file of water molecules, why are protons so effectively repelled? the answer is in the change of orientation of the water molecules inside the channel

Aquaporin simulation Structure, Dynamics, and Function of Aquaporins http://www.ks.uiuc.edu/Research/aquaporins/

The mechanism Upon entering, the water molecules face with their oxygen atom down the channel Midstream, they reverse orientation, facing with the oxygen atom up While passing through the channel, the single-file chain of water molecules streams through, always entering face down and leaving face up

human aquaporins brain kidneys lens fat tissues releases glycerol in fasting and starvation liver uptakes glycerol

aquaporins in tissues

Aquaporin 0 Differentiating lens fiber cells degrade their organelles and express a large amount of crystallins to create the correct refractive index. Light scattering is further minimized by the lack of blood vessels in the lens and by the tight packing of the fiber cells, which reduces the intercellular spaces to a distance smaller than the wavelength of visible light. Lens accommodation is accompanied by significant volume changes of the fiber cells, which require water to enter and exit fiber cells very rapidly, necessitating the presence of water pores in the fiber cell membranes.

Aquaporin simulation This illustration captures a snapshot of one of the largest atomic computational simulations ever attempted. The picture graphically depicts "boomerang-shaped" water molecules passing from outside of the cell (top blue area) to inside (bottom blue area) through an aquaporin pore (gold area) -- even as the cell membrane (red areas of diagram) provides an otherwise impermeable barrier between the cell's exterior and interior. Theoretical and Computational Biophysics Group at UIUC 2004 Winner of Visualization Challenge in Science and Engineering, Organized by the National Science Foundation and Science Magazine.

Aquaporins (AQPs) glycerol water

Glycerol in the GlpF channel

Open and closed conformations of the AQP0 water pore

Movie http://www.ks.uiuc.edu/Research/aquaporins/waterpermeation.mpg

glycerol forced to enter a pure water channel-side view

glycerol forced to enter a pure water channel-top view

summary of results

Conformational states of residue