一种内在的腺酸激酶活性调节了ABC输送器CFTR的关
Christoph Randak1, Michael J Welsh
1Howard 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
|December 31, 2003
概括
囊性纤维化转膜导电调节器 (CFTR) 蛋白质具有双重酶活性,同时作为ATPase和腺酸酶. 这种双重功能,特别是腺酸激酶活性,可以调节CFTR通道关,以最小的能量消耗.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生理学 细胞生理学
背景情况:
- 囊性纤维化跨膜导电调节器 (CFTR) 是一种离子通道,也是ATP结合盒 (ABC) 载体超级家族的成员.
- 由于阴离子运输的被动性,CFTR对ATP水解到离子流的要求一直令人困惑.
- 已知没有其他的离子通道可以利用ATP水解来封闭.
研究的目的:
- 为了研究CFTR除了简单的ATP水解之外的酶活性.
- 阐明CFTR通道封锁受管制的机制.
- 了解核酸结合域在CFTR功能中的作用.
主要方法:
- 生物化学测试用于检测和描述纯化CFTR的酶活性.
- 对ATP和AMP与CFTR相互作用的分析.
- 研究CFTR的ATPase和adenylate kinase活动的动力学.
主要成果:
- 除了已知的ATPase活性外,CFTR还表现出腺酸酶活性 (ATP + AMP <=> ADP + ADP).
- 腺酸酶活性显示出对ATP的积极合作性,这表明核酸结合域的潜在二元化.
- ATPase和腺酸酶活动都在第二个核酸结合域内共享一个共同的ATP结合位点.
结论:
- CFTR具有双重的酶功能,ATPase和腺酸酶,调节通道门.
- 在生理核酸度下,腺酸酶活性可能是CFTR门的主要调节者.
- 这种双重调节机制允许与仅依赖ATPase活动相比,具有潜在较低能耗的门控制.
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