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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >HYDROPHOBIC CLUSTER ANALYSIS PREDICTS AN AMINO-TERMINAL DOMAIN OF VARICELLA-ZOSTER VIRUS OPEN READING FRAME 10 REQUIRED FOR TRANSCRIPTIONAL ACTIVATION
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HYDROPHOBIC CLUSTER ANALYSIS PREDICTS AN AMINO-TERMINAL DOMAIN OF VARICELLA-ZOSTER VIRUS OPEN READING FRAME 10 REQUIRED FOR TRANSCRIPTIONAL ACTIVATION

机译:疏水性聚类分析预测了转录激活需要的水痘-ZOSTER病毒开放阅读框架10的氨基末端域

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摘要

Varicella-zoster virus open reading frame 10 (ORF10) protein, the homolog of the herpes simplex virus protein VP16, fan transactivate immediate-early promoters from both viruses. A protein sequence comparison procedure termed hydrophobic cluster analysis was used to identify a motif centered at Phe-28, near the amino terminus of ORF10, that strongly resembles the sequence of the activating domain surrounding Phe-442 of VP16. With a series of GAL4-ORF10 fusion proteins, we mapped the ORF10 transcriptional-activation domain to the amino-terminal region (aa 5-79). Extensive mutagenesis of Phe-28 in GAL4-ORF10 fusion proteins demonstrated the importance of an aromatic or bulky hydrophobic amino acid at this position, as shown previously for Phe-442 of VP16. Transactivation by the native ORF10 protein was abolished when Phe-28 was replaced by Ala. Similar amino-terminal domains were identified in the VP16 homologs of other alphaherpesviruses. Hydrophobic cluster analysis correctly predicted activation domains of ORF10 and VP16 that share critical characteristics of a distinctive subclass of acidic activation domains. [References: 34]
机译:水痘-带状疱疹病毒开放阅读框10(ORF10)蛋白是单纯疱疹病毒蛋白VP16的同源物,可扇形激活两种病毒的立即早期启动子。使用称为疏水簇分析的蛋白质序列比较程序来鉴定以ORF10氨基末端附近的Phe-28为中心的基序,该基序与VP16的Phe-442周围的激活域的序列非常相似。使用一系列GAL4-ORF10融合蛋白,我们将ORF10转录激活结构域定位到氨基末端区域(aa 5-79)。 GAL4-ORF10融合蛋白中Phe-28的广泛诱变表明,在该位置上芳香或庞大的疏水氨基酸的重要性,如先前对VP16的Phe-442所示。当Phe-28被Ala取代时,天然ORF10蛋白的反式激活被取消,在其他α疱疹病毒的VP16同源物中也鉴定出类似的氨基末端结构域。疏水聚类分析正确预测了ORF10和VP16的激活域,它们具有酸性激活域的独特子类的关键特征。 [参考:34]

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