ΔF508 mutation increases conformational flexibility of CFTR protein

BackgroundThe deletion of Phe508 in the first nucleotide-binding domain of the CFTR protein is the most common mutation leading to cystic fibrosis.MethodsWe present a Molecular Dynamics study on the native and mutated domains, based on their recently published crystal structure.ResultsΔF508 CFTR has much more conformational freedom compared to the wild-type, and exposes its hydrophobic interior to the solution.ConclusionsThe increased flexibility might be the reason for the recognition of mutated CFTR by the housekeeping proteins and its premature degradation. This, in turn results in reduction of population of functional channels at the epithelial cell surface and disease phenotype.