Rich D P, Gregory R J, Anderson M P, Manavalan P, Smith A E, Welsh M J
Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Science. 1991 Jul 12;253(5016):205-7. doi: 10.1126/science.1712985.
The cystic fibrosis transmembrane conductance regulator (CFTR), which forms adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, is defective in patients with cystic fibrosis. This protein contains two putative nucleotide binding domains (NBD1 and NBD2) and an R domain. CFTR in which the R domain was deleted (CFTR delta R) conducted chloride independently of the presence of cAMP. However, sites within CFTR other than those deleted also respond to cAMP, because the chloride current of CFTR delta R increased further in response to cAMP stimulation. In addition, deletion of the R domain suppressed the inactivating effect of a mutation in NBD2 (but not NBD1), a result which suggests that NBD2 interacts with the channel through the R domain.
形成3',5'-环磷酸腺苷（cAMP）调节性氯离子通道的囊性纤维化跨膜传导调节因子（CFTR）在囊性纤维化患者中存在缺陷。该蛋白包含两个推定的核苷酸结合结构域（NBD1和NBD2）和一个R结构域。缺失R结构域的CFTR（CFTR ΔR）可独立于cAMP的存在进行氯离子传导。然而，CFTR中除缺失位点以外的其他位点也对cAMP有反应，因为CFTR ΔR的氯离子电流在cAMP刺激下进一步增加。此外，R结构域的缺失抑制了NBD2（而非NBD1）中一个突变的失活作用，这一结果表明NBD2通过R结构域与通道相互作用。
