title: DeltaF508 mutation increases conformational flexibility of CFTR protein.
abstract: BACKGROUND
  The deletion of Phe508 in the first nucleotide-binding domain of the CFTR protein is the most common mutation leading to cystic fibrosis.
  
  
  METHODS
  We present a Molecular Dynamics study on the native and mutated domains, based on their recently published crystal structure.
  
  
  RESULTS
  DeltaF508 CFTR has much more conformational freedom compared to the wild-type, and exposes its hydrophobic interior to the solution.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warszawa, Poland. Electronic address: gigo@ibb.waw.pl.
authors.forename: G
authors.initials: G
authors.lastname: Wieczorek
authors.affiliation: Plant Molecular Biology Department, Warsaw University, Pawinskiego 5a, 02-106 Warszawa, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Zielenkiewicz
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D025341:Principal Component Analysis; D013329:Structure-Activity Relationship
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator