"Requirements for Efficient Correction of ΔF508 CFTR Revealed by Analyses of Evolved Sequences"

Mendoza, et. al.

Cystic fibrosis is a disease in which the chloride ion channels become defective. The ion channel that would function in a normal cell for the passage of chloride ions is termed the cystic fibrosis transmembrane conductance regulator (CFTR). The most common cause of cystic fibrosis is the result of the deletion of phenylalanine at the position 508 in the first nucleotide binding domain (NBD1). NBD1 gates the channel through the binding of ATP and hydrolysis reactions.

The study demonstrates this F508 deletion results in a misfolding of CFTR that renders the protein dysfunctional and hinders its maturation process. As a remedy, the study looks at potential mutations that could be applied in the form of binding compounds that would have the effect of both restoring the defective NBD1 and restoring the maturation process of the CFTR to ultimately treat the condition.