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Researchers get close-up view of water pores needed in the eye's lens
Date:8/5/2013

l and forces it to close.

The research was a collaboration between investigators at the University of California, Irvine, and the Janelia Farm Research Campus in Ashburn, Va., a part of the Howard Hughes Medical Institute (HHMI). Drs. James Hall and Douglas Tobias led the effort at UC Irvine. Dr. Tamir Gonen led the effort at Janelia Farm.

In prior studies, Dr. Gonen had examined the atomic structure of the AQP0 protein by X-ray crystallography, which involves crystallizing a protein and bombarding it with X-rays. But X-ray crystallography does not work well for large groups of proteins or for proteins in motion. So in the new study, the researchers first used electron microscopy to view AQP0 and calmodulin bound together. Then they combined their microscopy and crystallography data to generate computerized models of how the two proteins interact and to identify the most critical amino acids (the building blocks for proteins) within AQP0. To test their models, they neutralized those amino acids one by one in the actual AQP0 channel.

The AQP0 channel is made up of four identical barrel-shaped units, bundled together side by side. The researchers found that in the presence of calcium, calmodulin binds to one unit and then another, as if grabbing a pair of reins. This makes the channel twist slightly, which causes just a few amino acids within each unit to slide into the channel's core and block the flow of water.

"Calmodulin essentially throws a molecular switch that moves in and out of the water pore, like the gate valve of a plumbing fixture," Dr. Hall said.

This new view of AQP0 could help lead to new approaches for treating cataract, Dr. Hall said. Cataracts are the most common cause of blindness worldwide. In the United States, they affect about 1 in 6 people over age 40 and half over age 80. Congenital cataracts (present from birth) affect about 1 in 5,000 American children.

Cataracts can be successfully t
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Contact: Jean Horrigan
neinews@nei.nih.gov
301-496-5248
NIH/National Eye Institute
Source:Eurekalert

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