Thomas Miranda, Dasgupta Jhimli, Zhang Yi, Chen Xiaojiang, Banks Lawrence
Tumour Virology Laboratory, I.C.G.E.B., Padriciano 99, 34012 Trieste, Italy.
Virology. 2008 Jul 5;376(2):371-8. doi: 10.1016/j.virol.2008.03.021. Epub 2008 May 2.
The E6 oncoproteins of the cancer-associated human papillomaviruses (high-risk HPV types) characteristically have a PDZ-binding motif at their extreme carboxy-termini. However, they interact with only some of the PDZ domain-containing proteins in the human proteome and, despite many of these proteins having multiple PDZ domains, they interact specifically through only one of those domains. Previous work has shown that the exact sequence of the C-terminal PDZ-binding motif of E6 affects substrate selection, and recently we have shown that an E6 residue peripheral to the binding motif also contributes to the specificity of binding. Here we show that substrate specificity of the HPV E6 PDZ binding is modulated both by the amino acid residues upstream of the binding domain and by the non-canonical residues within it. Using this data we have begun to construct a scheme of substrate preferences for E6 proteins from different HPV types.
与癌症相关的人乳头瘤病毒（高危型人乳头瘤病毒）的E6癌蛋白在其极端羧基末端具有典型的PDZ结合基序。然而，它们仅与人蛋白质组中一些含PDZ结构域的蛋白质相互作用，并且尽管这些蛋白质中有许多具有多个PDZ结构域，但它们仅通过其中一个结构域进行特异性相互作用。先前的研究表明，E6的C末端PDZ结合基序的确切序列会影响底物选择，最近我们发现结合基序外围的一个E6残基也有助于结合的特异性。在这里，我们表明HPV E6 PDZ结合的底物特异性受到结合结构域上游的氨基酸残基及其内部非经典残基的调节。利用这些数据，我们已开始构建不同HPV类型E6蛋白的底物偏好方案。
