囊性纤维化
环核苷酸结合域
生物发生
囊性纤维化跨膜传导调节器
计算生物学
蛋白质折叠
细胞生物学
折叠(DSP实现)
医学
增强剂
生物
生物信息学
生物化学
药理学
遗传学
基因
核苷酸
工程类
电气工程
作者
Tzyh Chang Hwang,Ineke Braakman,Peter van der Sluijs,Isabelle Callebaut
标识
DOI:10.1016/j.jcf.2022.09.010
摘要
The root cause of cystic fibrosis (CF), the most common life-shortening genetic disease in the Caucasian population, is the loss of function of the CFTR protein, which serves as a phosphorylation-activated, ATP-gated anion channel in numerous epithelia-lining tissues. In the past decade, high-throughput drug screening has made a significant stride in developing highly effective CFTR modulators for the treatment of CF. Meanwhile, structural-biology studies have succeeded in solving the high-resolution three-dimensional (3D) structure of CFTR in different conformations. Here, we provide a brief overview of some striking features of CFTR folding, function and pharmacology, in light of its specific structural features within the ABC-transporter superfamily. A particular focus is given to CFTR's first nucleotide-binding domain (NBD1), because folding of NBD1 constitutes a bottleneck in the CFTR protein biogenesis pathway, and ATP binding to this domain plays a unique role in the functional stability of CFTR. Unraveling the molecular basis of CFTR folding, function, and pharmacology would inspire the development of next-generation mutation-specific CFTR modulators.
科研通智能强力驱动
Strongly Powered by AbleSci AI