Department of Pediatrics, Yale SOM, 488 Norton Parkway, New Haven, CT 06511, USA.
Virol J. 2011 Sep 5;8:422. doi: 10.1186/1743-422X-8-422.
The carboxyl terminal of Epstein-Barr virus (EBV) ZEBRA protein (also termed BZLF-1 encoded replication protein Zta or ZEBRA) binds to both NF-κB and p53. The authors have previously suggested that this interaction results from an ankyrin-like region of the ZEBRA protein since ankyrin proteins such as IκB interact with NF-κB and p53 proteins. These interactions may play a role in immunopathology and viral carcinogenesis in B lymphocytes as well as other cell types transiently infected by EBV such as T lymphocytes, macrophages and epithelial cells.
Randomization of the ZEBRA terminal amino acid sequence followed by statistical analysis suggest that the ZEBRA carboxyl terminus is most closely related to ankyrins of the invertebrate cactus IκB-like protein. This observation is consistent with an ancient origin of ZEBRA resulting from a recombination event between an ankyrin regulatory protein and a fos/jun DNA binding factor. In silico modeling of the partially solved ZEBRA carboxyl terminus structure using PyMOL software demonstrate that the carboxyl terminus region of ZEBRA can form a polymorphic structure termed ZANK (ZEBRA ANKyrin-like region) similar to two adjacent IκB ankyrin domains.
Viral capture of an ankyrin-like domain provides a mechanism for ZEBRA binding to proteins in the NF-κB and p53 transcription factor families, and also provides support for a process termed "Ping-Pong Evolution" in which DNA viruses such as EBV are formed by exchange of information with the host genome. An amino acid polymorphism in the ZANK region is identified in ZEBRA from tumor cell lines including Akata that could alter binding of Akata ZEBRA to the p53 tumor suppressor and other ankyrin binding protein, and a novel model of antagonistic binding interactions between ZANK and the DNA binding regions of ZEBRA is suggested that may be explored in further biochemical and molecular biological models of viral replication.
EBV ZEBRA 蛋白的羧基末端（也称为 BZLF-1 编码的复制蛋白 Zta 或 ZEBRA）与 NF-κB 和 p53 结合。作者先前曾提出，这种相互作用是由于 ZEBRA 蛋白中的锚蛋白样区域所致，因为像 IκB 这样的锚蛋白与 NF-κB 和 p53 蛋白相互作用。这些相互作用可能在 B 淋巴细胞中的免疫病理学和病毒致癌作用以及 EBV 瞬时感染的其他细胞类型（如 T 淋巴细胞、巨噬细胞和上皮细胞）中发挥作用。
ZEBRA 末端氨基酸序列的随机化，随后进行统计分析表明，ZEBRA 羧基末端与无脊椎仙人掌 IκB 样蛋白的锚蛋白最密切相关。这一观察结果与 ZEBRA 的古老起源一致，这是由于锚蛋白调节蛋白和 fos/jun DNA 结合因子之间的重组事件所致。使用 PyMOL 软件对部分解决的 ZEBRA 羧基末端结构进行计算机建模表明，ZEBRA 的羧基末端区域可以形成一种称为 ZANK（ZEBRA ANKyrin-like region）的多态结构，类似于两个相邻的 IκB 锚蛋白结构域。
病毒捕获锚蛋白样结构域为 ZEBRA 与 NF-κB 和 p53 转录因子家族中的蛋白质结合提供了一种机制，也为一种称为“乒乓进化”的过程提供了支持，在该过程中，EBV 等 DNA 病毒通过与宿主基因组交换信息而形成。在包括 Akata 在内的肿瘤细胞系中的 ZEBRA 中发现了 ZANK 区域的氨基酸多态性，这可能改变 Akata ZEBRA 与 p53 肿瘤抑制因子和其他锚蛋白结合蛋白的结合，并且提出了一种 ZANK 与 ZEBRA 的 DNA 结合区域之间拮抗结合相互作用的新模型，该模型可能在进一步的病毒复制生化和分子生物学模型中得到探索。
