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Scientists document water molecule movement across cell walls

Jim Barlow, Life Sciences Editor
(217) 333-5802; b-james3@uiuc.edu

4/18/02

UI scientists have documented a ballet in which dancers cross the stage in a billionth of a second.

CHAMPAIGN, Ill. — Scientists have documented a ballet in which dancers cross the stage in a billionth of a second. The stage is a class of proteins found in all living things; the dancers are water molecules. The performance, captured by supercomputer simulation, casts new insight for biomedical researchers on the controlled movement of water through cell walls.

Reporting in the April 19 issue of Science, researchers at the University of Illinois Beckman Institute for Advanced Science and Technology and at the University of California at San Francisco say the orientation of water molecules moving through aquaporins assures that only water, not ions such as protons, permeates between cells. If the latter occurs, energy stored as electrical potential between the inside and outside of the cell wall is lost.

Aquaporins, a class of proteins, form transmembrane channels found in cell walls. Plants have 35 different proteins of this type. Mammals, including humans, have 10, with many of them in the kidney, brain and lens of the eye.

When working correctly, said Klaus Schulten, the Swanlund Professor of Physics at the UI, the transport of water between plant cells lets flowers bloom and leaves stand sturdily, for example. In mammals, the machinery processes water efficiently to help maintain optimum health. A breakdown in human kidneys, the busiest water-handling organ with 400 liters being pumped through daily, leads to diabetes insipidus, in which water is not reabsorbed and abnormally large volumes of dilute urine are produced. Breakdowns in other organs can lead to loss of hearing and cataracts.

The structure of aquaporins was determined two years ago by Robert M. Stroud and colleagues at UCSF, who determined the geometry of the protein in the bacterium E. coli (GlpF).

However, Shulten said, that work "still could not resolve exactly how water is conducted in the channel, and how it prevents the conduction of ions." Crystallographic methods available today cannot capture such minute detail, he said.

Schulten collaborated with UI colleagues Emad Tajkhorshid, a senior postdoctoral researcher at the Beckman Institute, and Morten Jensen, a visiting doctoral student from Denmark. Using the largest computers available to civilian scientists in the United States, they simulated the channel, membrane and water on both sides, comprising a system of more than 100,000 atoms.

"This was one of the most advanced biomolecular simulations ever done," Schulten said, "made possible through support from computer scientists to run our programs on thousands of processors. We were able to see that water conducts very quickly, where exactly the water is located, and how the conduction of protons is prevented."

The simulations revealed that water molecules pass the channel single-file. 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 ballet 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, while still permitting a fast flux," Schulten said. "If these channels were leaky for ions, the electrical potentials of the cell walls would be abolished, leading to a complete breakdown of cell metabolism."

More information, including color graphics from the simulation, is available at www.ks.uiuc.edu/Research/aquaporins. The Web site is part of an NIH-funded Resource for Macromolecular Modeling and Bioinformatics Web site at the Beckman Institute.

UCSF participants in the study were Stroud, a co-principal investigator with Schulten, and Peter Nollert, Larry J.W. Miercke and Joseph O’Connell.