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Altering intracellular pH reveals the kinetic basis of intraburst gating in the CFTR Cl− channel

机译:改变细胞内pH揭示了CFTR Cl-通道内爆发门控的动力学基础

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Key points class="unordered" style="list-style-type:disc" id="tjp12084-list-0001">The cystic fibrosis transmembrane conductance regulator (CFTR), which is defective in the genetic disease cystic fibrosis (CF), forms a gated pathway for chloride movement regulated by intracellular ATP.To understand better CFTR function, we investigated the regulation of channel openings by intracellular pH.We found that short‐lived channel closures during channel openings represent subtle changes in the structure of CFTR that are regulated by intracellular pH, in part, at ATP‐binding site 1 formed by the nucleotide‐binding domains.Our results provide a framework for future studies to understand better the regulation of channel openings, the dysfunction of CFTR in CF and the action of drugs that repair CFTR gating defects.
机译:关键点 class =“ unordered” style =“ list-style-type:disc” id =“ tjp12084-list-0001”> <!-list-behavior = unordered prefix-word = mark-type = disc max- label-size = 0-> 在遗传疾病囊性纤维化(CF)中存在缺陷的囊性纤维化跨膜电导调节剂(CFTR)形成了由细胞内ATP调节的氯化物运动的门控途径。 为了更好地了解CFTR功能,我们研究了细胞内pH对通道开放的调节。 我们发现,通道开放过程中短暂的通道关闭代表CFTR结构的微妙变化,而CFTR的结构受到调节细胞内pH值部分位于核苷酸结合结构域形成的ATP结合位点1。 我们的结果为将来的研究提供了一个框架,以更好地了解CF中CFTR的功能性和开放性。以及修复CFTR门控缺陷的药物的作用。

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