Accessory Protein Facilitated CFTR-CFTR Interaction, a Molecular Mechanism to Potentiate the Chloride Channel Activity

Accessory Protein Facilitated CFTR-CFTR Interaction, a Molecular Mechanism to Potentiate the Chloride Channel Activity
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辅助蛋白促进 CFTR-CFTR 相互作用,增强氯离子通道活性的分子机制

DOI:
10.1016/s0092-8674(00)00096-9
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发表时间:
2000
期刊:
影响因子:
64.5
通讯作者:
Min Li
Min Li
中科院分区:
生物学1区
文献类型:
--
作者:
Shusheng Wang;Hongwen Yue;Rachel Derin;W. Guggino;Min Li

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细胞黏附纤维蛋白跨膜电导调节器(CFTR)基因编码一种氯通道蛋白,属于ATP结合盒(ABC)转运蛋白超家族。在三磷酸腺苷存在的情况下,蛋白激酶A的磷酸化激活了CFTR介导的根尖膜氯电导。我们已经鉴定出一种新的亲水性CFTR结合蛋白CAP70,它也集中在根尖表面。CAP70由四个PDZ结构域组成,其中三个能够与CFTR C末端结合。多价CAP70或二价单抗通过胞质C末端结合至少两个CFTR分子可增强CFTR氯通道的活性。因此,CFTR通道可以通过修饰分子间的CFTR-CFTR接触而切换到更活跃的传导状态,该修饰由辅助蛋白增强。
Thecysticfibrosistransmembrane conductanceregulator (CFTR) gene encodes a chloride channel protein that belongs to the superfamily ofATPbindingcassette (ABC) transporters. Phosphorylation by protein kinase A in the presence of ATP activates the CFTR-mediated chloride conductance of the apical membranes. We have identified a novel hydrophilic CFTR binding protein, CAP70, which is also concentrated on the apical surfaces. CAP70 consists of four PDZ domains, three of which are capable of binding to the CFTR C terminus. Linking at least two CFTR molecules via cytoplasmic C-terminal binding by either multivalent CAP70 or a bivalent monoclonal antibody potentiates the CFTR chloride channel activity. Thus, the CFTR channel can be switched to a more active conducting state via a modification of intermolecular CFTR-CFTR contact that is enhanced by an accessory protein.
DOI: 10.1172/jci115582
发表时间: 1992-01-01
影响因子: 15.9
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