Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis.
Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis.
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DOI：
10.1152/physrev.1999.79.1.s77
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发表时间：
1999
影响因子：
33.6
通讯作者：
D. Gadsby;A. Nairn
中科院分区：
文献类型：
--
作者：
D. Gadsby;A. Nairn
通过磷酸化和核苷酸水解控制CTFR通道门控。生理学修订版79，增补：S77-S107，1999年。- 囊性纤维化跨膜传导调节因子（CFTR）Cl-通道是囊性纤维化中基因缺陷的蛋白产物，囊性纤维化是高加索人中最常见的致死性遗传疾病。与任何其他已知的离子通道不同，CFTR属于转运蛋白的ATP结合盒超家族，并且与所有其他家族成员一样，CFTR包括两个细胞质核苷酸结合结构域（NBD），这两个结构域都结合并水解ATP。似乎在单个开闭门控循环中，单个CFTR通道水解NH 2末端NBD处的一个ATP分子以打开通道，然后结合并水解COOH末端NBD处的第二个ATP分子以关闭通道。两个NBD的这种复杂的协调行为是由多个蛋白激酶A依赖性磷酸化事件协调的，其中至少有一些发生在第三个大的胞质结构域（称为调节结构域）内。两种或两种以上的蛋白磷酸酶选择性地使不同的位点去磷酸化。在进行性磷酸化或去磷酸化的适当控制条件下，可以基于通道开放和关闭动力学来区分单个CFTR通道的三种功能上不同的磷酸形式。记录单个CFTR通道电流提供了一个前所未有的机会，可重复地检查，并操纵，在一个单一的分子，在其自然环境中，在真实的时间的个人ATP水解周期。
Control of CTFR Channel Gating by Phosphorylation and Nucleotide Hydrolysis. Physiol. Rev. 79, Suppl.: S77-S107, 1999. - The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel is the protein product of the gene defective in cystic fibrosis, the most common lethal genetic disease among Caucasians. Unlike any other known ion channel, CFTR belongs to the ATP-binding cassette superfamily of transporters and, like all other family members, CFTR includes two cytoplasmic nucleotide-binding domains (NBDs), both of which bind and hydrolyze ATP. It appears that in a single open-close gating cycle, an individual CFTR channel hydrolyzes one ATP molecule at the NH2-terminal NBD to open the channel, and then binds and hydrolyzes a second ATP molecule at the COOH-terminal NBD to close the channel. This complex coordinated behavior of the two NBDs is orchestrated by multiple protein kinase A-dependent phosphorylation events, at least some of which occur within the third large cytoplasmic domain, called the regulatory domain. Two or more kinds of protein phosphatases selectively dephosphorylate distinct sites. Under appropriately controlled conditions of progressive phosphorylation or dephosphorylation, three functionally different phosphoforms of a single CFTR channel can be distinguished on the basis of channel opening and closing kinetics. Recording single CFTR channel currents affords an unprecedented opportunity to reproducibly examine, and manipulate, individual ATP hydrolysis cycles in a single molecule, in its natural environment, in real time.