Altered protein folding may be the molecular basis of most cases of cystic fibrosis.
Experiments have demonstrated that the cystic fibrosis transmembrane conductance regulator protein (CFTR), containing the most common cystic fibrosis (CF)-causing mutation (delta F508), reaches the plasma membrane in reduced amounts. Studies of a peptide model of CFTR indicate that the delta F508 mutated region is more sensitive to denaturating conditions. This paper proposes that altered protein folding accounts for these findings, and, thus, most cases of CF. Significantly, the hypothesis makes specific predictions about the effect of stabilizing conditions on mutant CFTR, and, further, suggests a new class of pharmaceuticals that may prove effective in the treatment of this important genetic disease.
Thomas
P J
PJ
Department of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
Ko
Y H
YH
Pedersen
P L
PL
D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D014176:Protein Biosynthesis; D017510:Protein Folding
C505032:CFTR protein, human; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator