PhD defense: Uncovering CFTR folding through patient mutations

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 have employed the Cystic Fibrosis transmembrane conductance regulator (CFTR) as a model protein for studying ABC-transporter folding. CFTR is a chloride channel defective in the disease Cystic Fibrosis. To define folding mechanisms of CFTR we subjected cells expressing a suite of CFTR patient mutations to radiolabeling, marking the CFTR protein. At several stages during folding we investigated the conformation of the mutant proteins. The results now allow predictions on how CFTR folds and on the effect of a patient mutation.