Kanelis Voula, Chong P Andrew, Forman-Kay Julie D
Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada.
Methods Mol Biol. 2011;741:377-403. doi: 10.1007/978-1-61779-117-8_25.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a multi-domain membrane chloride channel whose activity is regulated by ATP at two nucleotide-binding domains (NBD1 and NBD2) and by phosphorylation of the regulatory (R) region. The NBDs and the R region have functionally relevant motions that are critical for channel gating. Nuclear magnetic resonance (NMR) spectroscopy is a highly useful technique for obtaining information on the structure and interactions of CFTR and is extremely powerful for probing dynamics. NMR approaches for studying CFTR are reviewed, using our previous NBD1 and the R region results to provide examples. These NMR data are yielding insights into the dynamic properties and interactions that facilitate normal CFTR regulation as well as pathological effects of mutations, including the most common disease mutant, deletion of F508 in NBD1.
囊性纤维化跨膜传导调节因子（CFTR）是一种多结构域膜氯离子通道，其活性在两个核苷酸结合结构域（NBD1和NBD2）受ATP调节，并受调节（R）区域磷酸化的影响。NBDs和R区域具有功能相关的运动，这对通道门控至关重要。核磁共振（NMR）光谱是一种非常有用的技术，可用于获取有关CFTR结构和相互作用的信息，并且在探测动力学方面极其强大。本文综述了研究CFTR的NMR方法，并以我们之前关于NBD1和R区域的结果为例进行说明。这些NMR数据正在深入了解促进正常CFTR调节的动态特性和相互作用，以及突变的病理效应，包括最常见的疾病突变体NBD1中F508的缺失。
