Altered protein folding may be the molecular basis of most cases of cystic fibrosis

作者：Philip Thomas, Young Hee Ko, Peter L. Pedersen · 发表于：FEBS Letters · 年份：1992 · DOI：10.1016/0014-5793(92)81399-7 · 被引用次数：70 · 研究领域：Cystic Fibrosis Research Advances、Advanced biosensing and bioanalysis techniques、Inhalation and Respiratory Drug Delivery

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.