Randak Christoph, Welsh Michael J
Howard Hughes Medical Institute, Department of Internal Medicine and Physiology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Cell. 2003 Dec 26;115(7):837-50. doi: 10.1016/s0092-8674(03)00983-8.
Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel in the ATP binding cassette (ABC) transporter family. Like other ABC transporters, it can hydrolyze ATP. Yet while ATP hydrolysis influences channel gating, it has long seemed puzzling that CFTR would require this reaction because anions flow passively through CFTR. Moreover, no other ion channel is known to require the large energy of ATP hydrolysis to gate. We found that CFTR also has adenylate kinase activity (ATP + AMP <=> ADP + ADP) that regulates gating. When functioning as an adenylate kinase, CFTR showed positive cooperativity for ATP suggesting its two nucleotide binding domains may dimerize. Thus, channel activity could be regulated by two different enzymatic reactions, ATPase and adenylate kinase, that share a common ATP binding site in the second nucleotide binding domain. At physiologic nucleotide concentrations, adenylate kinase activity, rather than ATPase activity may control gating, and therefore involve little energy consumption.
囊性纤维化跨膜传导调节因子（CFTR）是ATP结合盒（ABC）转运蛋白家族中的一种阴离子通道。与其他ABC转运蛋白一样，它能够水解ATP。然而，虽然ATP水解会影响通道门控，但长期以来CFTR需要这种反应一直令人费解，因为阴离子是被动通过CFTR的。此外，已知没有其他离子通道需要ATP水解产生的大量能量来进行门控。我们发现CFTR还具有调节门控的腺苷酸激酶活性（ATP + AMP <=> ADP + ADP）。当作为腺苷酸激酶发挥作用时，CFTR对ATP表现出正协同性，表明其两个核苷酸结合结构域可能会二聚化。因此，通道活性可以由两种不同的酶促反应——ATP酶和腺苷酸激酶来调节，它们在第二个核苷酸结合结构域中共享一个共同的ATP结合位点。在生理核苷酸浓度下，腺苷酸激酶活性而非ATP酶活性可能控制门控，因此能量消耗很少。
