Sheppard D N, Ostedgaard L S, Rich D P, Welsh M J
Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Cell. 1994 Mar 25;76(6):1091-8. doi: 10.1016/0092-8674(94)90385-9.
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel consists of two motifs (each containing a membrane-spanning domain [MSD] and a nucleotide-binding domain [NBD]) linked by an R domain. We tested the hypothesis that one MSD-NBD motif could form a Cl- channel. The amino-terminal portion of CFTR (D836X, which contains MSD1, NBD1, and the R domain) formed Cl- channels with conductive properties identical to those of CFTR. However, channel regulation differed. Although phosphorylation increased activity, channels opened without phosphorylation. MgATP stimulated D836X more potently than CFTR and may interact at more than one site. These data and migration of D836X on sucrose density gradients suggest that D836X may function as a multimer. Thus, the amino-terminal portion of CFTR contains all of the structures required to build a regulated Cl- channel.
囊性纤维化跨膜传导调节因子（CFTR）氯离子通道由两个基序（每个基序包含一个跨膜结构域[MSD]和一个核苷酸结合结构域[NBD]）通过一个R结构域相连组成。我们检验了一个假设，即一个MSD-NBD基序可以形成一个氯离子通道。CFTR的氨基末端部分（D836X，包含MSD1、NBD1和R结构域）形成了具有与CFTR相同导电特性的氯离子通道。然而，通道调节有所不同。虽然磷酸化增加了活性，但通道在没有磷酸化的情况下也会开放。MgATP对D836X的刺激比CFTR更强，并且可能在多个位点相互作用。这些数据以及D836X在蔗糖密度梯度上的迁移表明D836X可能作为多聚体发挥作用。因此，CFTR的氨基末端部分包含构建一个受调节的氯离子通道所需的所有结构。
