A defective flexible loop contributes to the processing and gating defects of the predominant cystic fibrosis‐causing mutation

What is it about?

Cystic fibrosis (CF) is a life-shortening autosomal recessive disease caused by mutations in the gene of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. About 90% of people with CF carry a mutation ΔF508 that deletes a phenylalanine residue at position 508 in CFTR and profoundly reduces protein expression and the channel activity. How the ΔF508 mutation initiates these two major functional defects is not well understood. Our data revealed that the G509 residue with position shifted one residue forward in a loop structure in ΔF508-CFTR was the primary mechanism that impairs protein expression and channel function. Therefore, this study highlights a possibility to cure ΔF508-associated CF diseases by exploring new drugs or treatments that correct loop abnormalities from the G509 displacement.

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