Complement yourself: Transcomplementation rescues partially folded mutant proteins.
Complement yourself: Transcomplementation rescues partially folded mutant proteins.
复制标题
补充自己：反式互补可挽救部分折叠的突变蛋白。
DOI：
10.1007/s12551-014-0137-3
复制
发表时间：
2014
影响因子：
--
通讯作者：
Guggino,WilliamB
中科院分区：
文献类型：
--
作者：
Cebotaru,Liudmila;Guggino,WilliamB
囊性纤维化（CF）是一种常染色体疾病，与跨多个粘膜的液体和电解质运输功能障碍有关。 CF 中最常见的突变是框内三碱基对缺失，删除了囊性纤维化电导调节因子 (CFTR) 氯离子通道第一个核苷酸结合域中第 508 位的苯丙氨酸。这种突变已被广泛研究，并导致内质网中蛋白质的生物合成停滞并严重降低通道活性。这篇综述讨论了一种通过反式互补拯救 ΔF508 的新方法，当含有野生型核苷酸结合域的 CFTR 较小片段与 F508 缺失突变体共表达时，就会发生这种情况。反式补体可恢复 ΔF508 的加工和通道活性，并降低其在气道上皮细胞中的降解率。要将反式互补作为一种疗法，需要将编码截短的 CFTR 的 cDNA 递送至细胞。我们还讨论了一种基于使用腺相关病毒载体将截短形式的 CFTR 递送至气道细胞的基因治疗方法。
Cystic fibrosis (CF) is an autosomal disease associated with malfunction in fluid and electrolyte transport across several mucosal membranes. The most common mutation in CF is an in-frame three-base pair deletion that removes a phenylalanine at position 508 in the first nucleotide-binding domain of the cystic fibrosis conductance regulator (CFTR) chloride channel. This mutation has been studied extensively and leads to biosynthetic arrest of the protein in the endoplasmic reticulum and severely reduced channel activity. This review discusses a novel method of rescuing ΔF508 with transcomplementation, which occurs when smaller fragments of CFTR containing the wild-type nucleotide binding domain are co-expressed with the F508 deletion mutant. Transcomplementation rescues the processing and channel activity of ΔF508 and reduces its rate of degradation in airway epithelial cells. To apply transcomplementation as a therapy would require that the cDNA encoding the truncated CFTR be delivered to cells. We also discuss a gene therapeutic approach based on delivery of a truncated form of CFTR to airway cells using adeno-associated viral vectors.