A map of WW domain family interactions
A map of WW domain family interactions
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DOI：
10.1002/pmic.200300632
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发表时间：
2004-03-01
期刊：
影响因子：
3.4
通讯作者：
Herrero, JJ
中科院分区：
文献类型：
--
作者：
Hu, H;Columbus, J;Herrero, JJ
WW结构域是结合富含脯氨酸的配体的蛋白质模块。WW结构域-配体复合物是重要的，因为它们涉及几种人类疾病，例如肌营养不良症、癌症、高血压、阿尔茨海默病和亨廷顿病。我们报告的蛋白质阵列的结果，旨在映射所有的人类WW域蛋白质-蛋白质相互作用。我们的生物化学方法集成了肽的平行合成，蛋白质表达和高通量筛选方法与生物信息学工具相结合。结果表明，大多数生物信息学预测的WW肽配体和大多数WW结构域是功能性的，并且只有约10%的测得的结构域-配体相互作用是正的。WW结构域蛋白阵列的分析还强调了WW配体核心基序周围的氨基酸残基对于特异性结合WW结构域的重要性。此外，这里提出的方法允许快速阐明WW结构域-配体相互作用，具有多种应用，包括精确的WW配体结合位点的预测，其可以应用于其他蛋白质信号传导结构域家族的映射。这些信息可以应用于蛋白质相互作用网络的生成和潜在药物靶点的识别。据我们所知，这份报告描述了第一个蛋白质-蛋白质相互作用图的一个域在人类蛋白质组。
WW domains are protein modules that bind proline-rich ligands. WW domain-ligand complexes are of importance as they have been implicated in several human diseases such as muscular dystrophy, cancer, hypertension, Alzheimer's, and Huntington's diseases. We report the results of a protein array aimed at mapping all the human WW domain protein-protein interactions. Our biochemical approach integrates parallel synthesis of peptides, protein expression, and high-throughput screening methodology combined with tools of bioinformatics. The results suggest that the majority of the bioinformatically predicted WW peptide ligands and most WW domains are functional, and that only about 10% of the measured domain-ligand interactions are positive. The analysis of the WW domain protein arrays also underscores the importance of the amino acid residues surrounding the WW ligand core motifs for specific binding to WW domains. In addition, the methodology presented here allows for the rapid elucidation of WW domain-ligand interactions with multiple applications including prediction of exact WW ligand binding sites, which can be applied to the mapping of other protein signaling domain families. Such information can be applied to the generation of protein interaction networks and identification of potential drug targets. To our knowledge, this report describes the first protein-protein interaction map of a domain in the human proteome.