Mutations at many sites within the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel pore region result in changes in chloride conductance. Although chloride binding in the pore – as well as interactions between concurrently bound chloride ions – are thought to be important facets of the chloride permeation mechanism, little is known about the relationship between anion binding and chloride conductance. The present work presents a comprehensive investigation of a number of anion binding properties in different pore mutants with differential effects on chloride conductance. When multiple pore mutants are compared, conductance appears best correlated with the ability of anions to bind to the pore when it is already occupied by chloride ions. In contrast, conductance was not correlated with biophysical measures of anion:anion interactions inside the pore. Although these findings suggest anion binding is required for high conductance, mutations that strengthened anion binding had very little effect on conductance, especially at high chloride concentrations, suggesting that the wild-type CFTR pore is already close to saturated with chloride ions. These results are used to support a revised model of chloride permeation in CFTR in which the overall chloride occupancy of multiple loosely-defined chloride binding sites results in high chloride conductance through the pore.

囊性纤维化跨膜电导调节剂（CFTR）氯化物通道孔区域内许多部位的突变都会导致氯化物电导率的变化。尽管氯在孔中的结合以及同时结合的氯离子之间的相互作用被认为是氯渗透机制的重要方面，但对阴离子结合与氯电导之间的关系知之甚少。本工作提出了对不同的孔突变体中的许多阴离子结合特性的全面研究，这些特性对氯离子的传导具有不同的影响。当比较多个孔突变体时，当氯已被氯离子占据时，电导似乎与阴离子与孔的结合能力最相关。相反，电导率与阴离子的生物物理测量值无关：孔内的阴离子相互作用。尽管这些发现表明高电导需要阴离子结合，但是增强阴离子结合的突变对电导的影响很小，尤其是在高氯浓度下，这表明野生型CFTR孔已经接近被氯离子饱和的状态。这些结果用于支持CFTR中氯离子渗透的修正模型，其中多个松散定义的氯离子结合位点的总氯离子占据导致通过孔的高氯离子传导。这表明野生型CFTR孔已经接近氯离子饱和。这些结果用于支持CFTR中氯离子渗透的修正模型，其中多个松散定义的氯离子结合位点的总氯离子占据导致通过孔的高氯离子传导。这表明野生型CFTR孔已经接近氯离子饱和。这些结果用于支持CFTR中氯离子渗透的修正模型，其中多个松散定义的氯离子结合位点的总氯离子占据导致通过孔的高氯离子传导。