Uncovering CFTR folding through patient mutations

The ABC-transporter protein family has a diverse set of functions in all domains of life and several family members are implicated in disease. We employ the Cystic Fibrosis transmembrane conductance regulator (CFTR) as a model protein for studying ABC-transporter folding. CFTR is a chloride channel involved in the disease Cystic Fibrosis. To define folding mechanisms of CFTR we subjected cell expressing a suite of patient mutations and labeled the CFTR protein. At several stages in folding we investigated the conformation of the different mutant proteins, that are known to form a functionally defective protein. Based on the results predictions can now be made on how the protein folds.