A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator
A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator
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DOI：
10.1021/bi0108195
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发表时间：
2001-09-04
期刊：
影响因子：
2.9
通讯作者：
Bear, CE
中科院分区：
文献类型：
--
作者：
Ramjeesingh, M;Li, CH;Bear, CE
囊性纤维化跨膜传导调节因子（CFTR）通常作为上皮细胞顶端表面上的磷酸化调节的氯离子通道起作用，并且缺乏这种功能是致命疾病囊性纤维化（CF）的主要原因。以前的研究表明，纯化的，重建的CFTR可以作为氯离子通道和。进一步.其内在的ATP酶活性是调节通道门的打开和关闭所必需的。然而.这些先前的研究没有确定介导传导和催化所需的四级结构。我们目前的研究表明，CFTR分子可以在CHO和Sf9膜中自缔合，因为接近CFTR二聚体预测大小的复合物可以通过化学交联试剂捕获并使用非解离PAGE检测。然而，CFTR功能不需要多聚体复合物的功能，因为我们确定纯化。重构的CFTR单体足以介导调节的氯离子传导和ATP酶活性。
The cystic fibrosis transmembrane conductance regulator (CFTR) normally functions as a phosphorylation-regulated chloride channel on the apical surface of epithelial cells, and lack of this function is the primary cause for the fatal disease cystic fibrosis (CF). Previous studies showed that purified, reconstituted CFTR can function as a chloride channel and. further. that its intrinsic ATPase activity is required to regulate opening and closing of the channel gate. However. these previous studies did not identify the quaternary structure required to mediate conduction and catalysis. Our present studies show that CFTR molecules may self-associate in CHO and Sf9 membranes, as complexes close to the predicted size of CFTR dimers can be captured by chemical cross-linking reagents and detected using nondissociative PAGE. However, CFTR function does not require a multimeric complex for function as we determined that purified. reconstituted CFTR monomers are sufficient to mediate regulated chloride conduction and ATPase activity.