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Cystic Fibrosis Proteins Photographed Interacting

New microscopic pictures show the first-ever physical evidence of interaction between two proteins involved in Cystic Fibrosis (CF) disease.

Researchers at the University of Alabama at Birmingham (UAB) studied a CF-causing protein and another protein called epithelial sodium channel, or ENaC. Both proteins are known to play a role in CF, but exactly what role each plays is unclear.

The new pictures provide physical proof that these two proteins occur close enough to interact with each other, the UAB researchers said. When that interaction fails then a dangerous biochemical imbalance occurs in people diagnosed with CF.

Knowing more about this protein proximity will help scientists better understand the biological underpinnings of CF and may speed the discovery of new drugs to treat or cure the disease. CF affects 70,000 people worldwide, 30,000 in the United States.

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The findings are published in the Journal of Biological Chemistry, which included a color photo from the UAB study on its cover.

“Our findings suggest a direct interaction between these two proteins and their proximity makes the evidence convincing,” said Bakhrom Berdiev, M.D., Ph.D., a UAB assistant professor of cell biology and lead author on the study.

The study was conducted using a laser-scanning microscope that captured images of the two proteins “within reach of each other. The absence of this interaction could shape the development of CF,” Berdiev said.

Normally, both proteins help make up the lining of the lungs and other membranes, and keep the balance of water and salt at safe levels. In the case of CF, ENaC is allowed to hyper-function in the presence of the CF-causing protein and disturb the balance of water and salt.

When this happens, a sticky mucus usually forms inside the airways which can lead to chronic lung infections, the most dangerous symptom of CF. Other symptoms involve digestive problems.

With the discovery of the CF gene in 1989, many scientists began searching for ways to repair the DNA or repair the faulty protein encoded by the DNA.

The new Journal of Biological Chemistry study shows that future research should look at other molecules not directly linked to CF but are involved in the disease process and its side effects, Berdiev said.

Also, the new pictures add to an ever-changing biophysical “map” of CF used to design future research.

The new pictures were done through collaboration between UAB’s departments of Cell Biology, Physiology & Biophysics, High Resolution Imaging Facility and the Gregory Fleming James Cystic Fibrosis Research Center at UAB. Other collaborators are from Ohio State University, the University of Toronto, Ontario, the National Heart Lung and Blood Institute in Bethesda, Maryland and Lambert Instruments in the Netherlands.

Funding for the study came from the National Institutes of Health and the Cystic Fibrosis Foundation.

Troy Goodman | EurekAlert!
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