Defect in cystic fibrosis protein found.

Biochemists studying a specific genetic mutation that causes most cases of cystic fibrosis have come up with a new lead in understanding the disease.

Peter L. Pedersen and his colleagues at the Johns Hopkins University School of Medicine in Baltimore have found that the mutation leads to the deletion of a crucial amino acid from the protein involved in the disease. The protein, cystic fibrosis transmembrane conductance regulator (CFTR), usually helps cells maintain normal levels of chloride. But Pedersen's group found that when the protein lacks this amino acid, it doesn't fold into its correct shape and loses its function. The mucus buildup of cystic fibrosis results. The researchers report their finding in the March 25 JOURNAL OF BIOLOGICAL CHEMISTRY.

Scientists first discovered the CFTR gene more than two years ago (SN: 9/2/89, p.149). Further studies indicated that mutations in the CFTR gene lead to defective CFTR proteins that cannot move from the interior of a cell, where they are made, to their places in the cell's outer membrane (SN: 11/24/90, p.324).

Pedersen's group confirmed that mutant CFTR proteins have a three-dimensional shape that differs from normal CFTR proteins. They also showed that this altered shape prevents the mutant proteins from binding to ATP, the molecule that usually provides them with chemical fuel.

Pedersen says his group's finding suggests that structure-correcting proteins called "chaperonins" offer promise as drugs to straighten out the CFTR defects behind cystic fibrosis. Chaperonins play a natural role in reshaping mutant proteins and in keeping newly made proteins from tangling.