Infected cell protein 0 (ICP0) is an immediate‐early regulatory protein of herpes simplex virus 1 (HSV‐1) that possesses E3 ubiquitin ligase activity. ICP0 transactivates viral genes, in part, through its C‐terminal dimer domain (residues 555–767). Deletion of this dimer domain results in reduced viral gene expression, lytic infection, and reactivation from latency. Since ICP0's dimer domain is associated with its transactivation activity and efficient viral replication, we wanted to determine the structure of this specific domain. The C‐terminus of ICP0 was purified from bacteria and analyzed by X‐ray crystallography to solve its structure. Each subunit or monomer in the ICP0 dimer is composed of nine β‐strands and two α‐helices. Interestingly, two adjacent β‐strands from one monomer “reach” into the adjacent subunit during dimer formation, generating two β‐barrel‐like structures. Additionally, crystallographic analyses indicate a tetramer structure is formed from two β‐strands of each dimer, creating a “stacking” of the β‐barrels. The structural protein database searches indicate the fold or structure adopted by the ICP0 dimer is novel. The dimer is held together by an extensive network of hydrogen bonds. Computational analyses reveal that ICP0 can either form a dimer or bind to SUMO1 via its C‐terminal SUMO‐interacting motifs but not both. Understanding the structure of the dimer domain will provide insights into the activities of ICP0 and, ultimately, the HSV‐1 life cycle.

中文翻译：

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HSV-1 ICP0 二聚体结构域采用新型 β 桶折叠

感染细胞蛋白 0 (ICP0) 是单纯疱疹病毒 1 (HSV-1) 的立即早期调节蛋白，具有 E3 泛素连接酶活性。ICP0 部分地通过其 C 末端二聚体结构域（残基 555-767）反式激活病毒基因。删除该二聚体结构域会导致病毒基因表达减少、裂解性感染和潜伏期重新激活。由于 ICP0 的二聚体结构域与其反式激活活性和有效的病毒复制相关，因此我们想要确定该特定结构域的结构。从细菌中纯化出 ICP0 的 C 末端，并通过 X 射线晶体学分析来解析其结构。ICP0 二聚体中的每个亚基或单体由九个 β 链和两个 α 螺旋组成。有趣的是，在二聚体形成过程中，一个单体的两个相邻的 β 链“到达”相邻的亚基，产生两个 β 桶状结构。此外，晶体学分析表明四聚体结构是由每个二聚体的两条 β 链形成的，从而形成 β 桶的“堆叠”。结构蛋白数据库检索表明ICP0二聚体采用的折叠或结构是新颖的。二聚体通过广泛的氢键网络连接在一起。计算分析表明，ICP0 可以形成二聚体，也可以通过其 C 端 SUMO 相互作用基序与 SUMO1 结合，但不能两者兼而有之。了解二聚体结构域的结构将有助于深入了解 ICP0 的活动，并最终了解 HSV-1 的生命周期。