Qu B H, Strickland E, Thomas P J
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 75235-9040, USA.
J Bioenerg Biomembr. 1997 Oct;29(5):483-90. doi: 10.1023/a:1022439108101.
Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator, CFTR. Previously we demonstrated that the common delta F508 mutation in the first nucleotide binding domain (NBD1) alters the ability of the domain to fold into a functional three-dimensional structure, providing a molecular explanation for the observation that the mutant CFTR is retained in the endoplasmic reticulum and does not traffic to the apical membrane of affected epithelial cells. Notably, when conditions are altered to promote folding of the mutant protein, it can assume a functional conformation. Correcting the folding defect may have therapeutic benefit for the treatment of cystic fibrosis. Here we summarize these results and discuss the implications in vitro folding studies have for understanding the pathobiology of CF.
囊性纤维化（CF）由编码囊性纤维化跨膜传导调节因子（CFTR）的基因突变引起。此前我们证明，第一个核苷酸结合结构域（NBD1）中常见的ΔF508突变改变了该结构域折叠成功能性三维结构的能力，这为突变型CFTR保留在内质网中且不转运至受影响上皮细胞的顶端膜这一现象提供了分子解释。值得注意的是，当改变条件以促进突变蛋白折叠时，它可以呈现功能性构象。纠正折叠缺陷可能对囊性纤维化的治疗具有治疗益处。在此我们总结这些结果，并讨论体外折叠研究对理解CF病理生物学的意义。
