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

FEBS Letters

Pedersen, Peter L.¹  Ko, Young H.¹  Thomas, Philip J.¹ 

[1] Department of Biological Chemistry, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA

关键词: Cystic fibrosis;    Cystic fibrosis transmembrane conductance regulator (CFTR);    Protein folding;    Genetic disease;   

DOI  :  10.1016/0014-5793(92)81399-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Experiments have demonstrated that the cystic fibrosis transmembrane conductance regulator protein (CFTR), containing the most common cystic fibrosis (CF)-causing mutation (ΔF508), reaches the plasma membrane in reduced amounts. Studies of a peptide model of CFTR indicate that the ΔF508 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.

【 授权许可】

Unknown