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UI researchers discover new activity in cystic fibrosis protein

Even well-studied proteins can reveal surprises. University of Iowa scientists have discovered a new enzyme activity for the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is the protein that is defective in cystic fibrosis, a common life-threatening genetic disease that affects primarily the lungs and pancreas of young people. The discovery, which appeared in the Dec. 26, 2003 issue of Cell, helps solve a long-standing puzzle about how this important protein works.

CFTR forms a channel, or pore, in the membrane of airway cells. When the channel is open, the salt chloride flows through it from one side of the membrane to the other. It has been known for many years that CFTR channel opening requires a molecule called ATP and that CFTR has an enzymatic activity called ATPase that uses ATP. ATP is the energy currency of the cell and the ATPase reaction spends the energy of ATP to power enzyme activity. Because chloride flows passively through the CFTR channel, it has long seemed puzzling that the opening of CFTR would require the substantial energy of ATP. Moreover, energy from ATP is not required to fuel any other ion channel.

The UI study now reveals that CFTR can function as an adenylate kinase enzyme. Like an ATPase, the adenylate kinase reaction uses ATP. But in contrast to an ATPase, an adenylate kinase enzyme also uses a related molecule called AMP. Importantly, the adenylate kinase neither consumes nor produces energy, but it controls channel opening. The study also suggests that in normal cells it is this enzyme activity rather than the ATPase that opens the CFTR channel.

"We think that in the normal physiologic context where AMP is present, CFTR would function as an adenylate kinase," said Christoph Randak, M.D., UI postdoctoral scholar in the UI Department of Internal Medicine and lead author of the study. "Thus, the CFTR channel may function without consuming a large amount of energy."

The UI study ma
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-335-9917
University of Iowa
27-Jan-2004


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