Department of Microbiology, University of Iowa, 3-712 BSB, Iowa City, IA 52242, USA.
J Virol. 2010 Apr;84(7):3542-51. doi: 10.1128/JVI.02570-09. Epub 2010 Jan 27.
The severe acute respiratory syndrome coronavirus (SARS-CoV) accessory protein 6 (p6) is a 63-amino-acid multifunctional Golgi-endoplasmic reticulum (ER) membrane-associated protein, with roles in enhancing virus replication and in evading the innate immune response to infection by inhibiting STAT1 (signal transducer and activator of transcription factor 1) translocation to the nucleus. Here, we demonstrate that p6 has an N-terminal region-cytoplasm-C-terminal region-cytoplasm configuration with residues 2 to 37 likely membrane embedded. Expression of p6, or of its N-terminal 41-amino-acid region, in the absence of other viral proteins, induced the formation of membranous structures, some of which were similar to double membrane vesicles involved in virus replication. Consistent with a role in virus replication, p6 partially colocalized with nonstructural protein 3 (nsp3), a marker for virus replication complexes. Further, while the C-terminal region is required for preventing STAT1 translocation to the nucleus, our results also indicated that the N-terminal 18 amino acids were necessary for maximal inhibition. Collectively, these results support the notion that p6 is a two-domain protein, although the function of each is not completely independent of the other.
严重急性呼吸综合征冠状病毒（SARS-CoV）辅助蛋白 6（p6）是一种 63 个氨基酸的多功能高尔基体-内质网（ER）膜相关蛋白，具有增强病毒复制和逃避感染固有免疫反应的作用，通过抑制 STAT1（信号转导和转录激活因子 1）易位到细胞核。在这里，我们证明 p6 具有 N 端区域-细胞质-C 端区域-细胞质的结构，其残基 2 至 37 可能嵌入膜中。p6 或其 N 端 41 个氨基酸区域的表达，在没有其他病毒蛋白的情况下，诱导膜结构的形成，其中一些与参与病毒复制的双膜囊泡相似。与病毒复制的作用一致，p6 部分与非结构蛋白 3（nsp3）共定位，nsp3 是病毒复制复合物的标志物。此外，虽然 C 端区域对于防止 STAT1 易位到细胞核是必需的，但我们的结果也表明，N 端的前 18 个氨基酸对于最大抑制是必需的。总之，这些结果支持 p6 是一种具有两个结构域的蛋白质的观点，尽管每个结构域的功能并不完全独立。
