All cancer-causing human papillomavirus (HPV) E6 oncoproteins have a C-terminal PDZ-binding motif (PBM), which correlates with oncogenic potential. Nonetheless, several HPVs with little or no oncogenic potential also have an E6 PBM, with minor sequence differences affecting PDZ protein selectivity. Furthermore, certain HPV types have a phospho-acceptor site embedded within the PBM. We therefore compared HPV-18, HPV-66 and HPV-40 E6 proteins to examine the possible link between the ability to target multiple PDZ proteins and the acquisition of a phospho-acceptor site. The mutation of essential residues in HPV-18E6 reduces its phosphorylation, and fewer PDZ substrates are bound. In contrast, the generation of consensus phospho-acceptor sites in HPV-66 and HPV-40 E6 PBMs increases the PDZ proteins recognized. Thus, although phosphorylation of the E6 PBM and PDZ protein recognition are mutually exclusive, they are closely linked, with the acquisition of a phospho-acceptor site also contributing to an expansion in the number of PDZ proteins bound.

中文翻译：

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磷酸受体位点的获得增强了HPV E6 PDZ结合基序功能的混杂。

所有引起癌症的人乳头瘤病毒（HPV）E6癌蛋白均具有C端PDZ结合基序（PBM），与致癌潜力相关。尽管如此，一些具有很少或没有致癌潜力的HPV也具有E6 PBM，序列差异较小会影响PDZ蛋白的选择性。此外，某些HPV类型在PBM中具有嵌入的磷酸受体位点。因此，我们比较了HPV-18，HPV-66和HPV-40 E6蛋白，以研究靶向多种PDZ蛋白的能力与磷酸受体位点的获得之间的可能联系。HPV-18E6中必需残基的突变降低了其磷酸化，并且结合的PDZ底物更少。相反，在HPV-66和HPV-40 E6 PBM中产生共有磷酸受体位点会增加公认的PDZ蛋白。从而，