Tyler J K, Allen K E, Everett R D
MRC Virology Unit, Glasgow, UK.
Nucleic Acids Res. 1994 Feb 11;22(3):270-8. doi: 10.1093/nar/22.3.270.
The product of varicella-zoster virus gene 62 (VZV 140k) is a potent transactivator protein. We have identified a region within the DNA binding domain of VZV 140k that shows a striking similarity to the DNA recognition helix of the homeodomain, with an especially highly conserved quartet of residues, WLQN. The 140k protein has functional counterparts within the other alphaherpesviruses, which include the major transcriptional regulatory protein of HSV-1, (ICP4), and the WLQN region is highly conserved among the members of this family of viral transactivators. Substitution of VZV 140k residue lysine 548, just adjacent to the WLQN region, drastically reduces the DNA binding activity of the 140k DNA binding domain and the intact 140k mutant protein fails to activate gene expression. Substitutions of two other VZV 140k residues in this conserved WLQN region result in alterations to the DNA binding interaction and reduced transactivation activities. All three mutations act at the level of DNA recognition, as they have no apparent effect on the dimerization state, solubility or efficiency of expression of the mutant peptides.
水痘-带状疱疹病毒基因62产物（VZV 140k）是一种有效的反式激活蛋白。我们在VZV 140k的DNA结合结构域内鉴定出一个区域，该区域与同源异型结构域的DNA识别螺旋具有显著相似性，有一组特别高度保守的残基WLQN。140k蛋白在其他甲型疱疹病毒中有功能对应物，包括单纯疱疹病毒1型的主要转录调节蛋白（ICP4），并且WLQN区域在该病毒反式激活蛋白家族成员中高度保守。紧邻WLQN区域的VZV 140k残基赖氨酸548的替换，极大地降低了140k DNA结合结构域的DNA结合活性，完整的140k突变蛋白无法激活基因表达。在这个保守的WLQN区域中另外两个VZV 140k残基的替换导致DNA结合相互作用的改变和反式激活活性的降低。所有这三个突变都在DNA识别水平起作用，因为它们对突变肽的二聚化状态、溶解度或表达效率没有明显影响。
