New Study Resolves Structure of Human Protein (CFTR) That Causes Cystic Fibrosis

Scientists at The Rockefeller University have mapped the three-dimensional structure for one of the more notorious disease-causing molecules in the human body: the protein responsible for the genetic disorder cystic fibrosis. In research described in the March 23, 2017 issue of Cell, the researchers report that the human structure is almost identical to one they have determined previously for the zebrafish version of the protein. The Cell article is titled “Molecular Structure of the Human CFTR Ion Channel.” “With these detailed new reconstructions, we can begin to understand how this protein functions normally, and how errors within it cause cystic fibrosis,” says Jue Chen, Ph.D., William E. Ford Professor at Rockefeller. “We now know that the conclusions we drew from our previous work in zebrafish also apply to us.” Cystic fibrosis arises from mutations in a single gene, which encodes a protein that forms a channel through which chloride ions pass in and out of cells. Errors in this protein, called the cystic fibrosis transmembrane conductance regulator (CFTR), can lead to the accumulation of thick, sticky mucus. The buildup of mucus has the deadliest effects in the lungs, where it can cause potentially fatal breathing problems or respiratory infections. Although cystic fibrosis is a human disorder, many animals also express CFTR. When the human protein proved difficult to work with in the lab, Dr. Chen and her colleagues instead turned to the more-cooperative zebrafish version. Among other things, they used it to map the location of disease-causing mutations—findings that can now be applied to studying how the faulty human protein can spark disease.
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