摘要
PDZ结构域通过促进蛋白质支架和蛋白复合物组装,在许多细胞过程中起着至关重要的作用。这些结构域由80-90个氨基酸组成,发现其能识别短的靶蛋白C-末端氨基酸序列。PDZ目标分子之间的蛋白复合物构型能形成很多信号和调控通路,这些通路可以促进或抑制某些蛋白的活化。有研究表明NHERF2的PDZ结构域与LPA2相互作用能通过促进CFTR–NHERF2–LPA2复杂装配对囊性纤维化跨膜传导调节(CFTR)起着抑制作用。有研究表明NHERF2的PDZ结构域与LPA2相互作用能通过促进CFTR–NHERF2–LPA2复杂装配对囊性纤维化跨膜传导调节(CFTR)起着抑制作用。这种疾病被称为囊性纤维化。因此,关注PDZ结构域的结构以及它形成的高分子复合物的功能,能增强CF患者CFTR通道的活性,这可能是重要的治疗方法。在这里,我们分析了PDZ结构域在CFTR调控囊性纤维化的结构,功能和意义并综述了PDZ结构域家族。
关键词: 囊性纤维化跨膜电导调节因子(CFTR),囊性纤维化,药物设计,NHERF1/2,PDZ,结构
Current Drug Targets
Title:PDZ Structure and Implication in Selective Drug Design against Cystic Fibrosis
Volume: 16 Issue: 9
Author(s): Joshua Holcomb, Nicholas Spellmon, Laura Trescott, Fei Sun, Chunying Li and Zhe Yang
Affiliation:
关键词: 囊性纤维化跨膜电导调节因子(CFTR),囊性纤维化,药物设计,NHERF1/2,PDZ,结构
摘要: PDZ domains play an essential role in a number of cellular processes by facilitating protein scaffolding and assembly of protein complexes. These domains consist of 80 to 90 amino acids and are found to recognize short C-terminal sequences of target proteins. Protein complex formation between PDZ target molecules can lead to a number of signaling and regulatory cascades that may either promote or inhibit the activation of certain proteins. It has been shown that the interaction of the PDZ domains of NHERF2 with LPA2 plays an inhibitory role on the cystic fibrosis transmembrane conductance regulator (CFTR) by promoting the assembly of a CFTR–NHERF2–LPA2 complex. CFTR regulates chloride ion transport across the epithelial plasma membrane, and individuals possessing CFTR mutations show decreased protein function and consequently, viscous mucus accumulation due to improper fluid transport. This type of ailment is termed cystic fibrosis. Thus, insight to the structure of PDZ domains and how they function to form macromolecular complexes could be therapeutically important in augmenting CFTR channel activity in cystic fibrosis patients. Here we review the PDZ domain family while dissecting their structure, function and implications in CFTR regulation and cystic fibrosis.
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Cite this article as:
Joshua Holcomb, Nicholas Spellmon, Laura Trescott, Fei Sun, Chunying Li and Zhe Yang , PDZ Structure and Implication in Selective Drug Design against Cystic Fibrosis, Current Drug Targets 2015; 16 (9) . https://dx.doi.org/10.2174/1389450116666141219120125
DOI https://dx.doi.org/10.2174/1389450116666141219120125 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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