Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
J Gen Virol. 2010 Jun;91(Pt 6):1524-34. doi: 10.1099/vir.0.018580-0. Epub 2010 Feb 10.
Gene m164 of murine cytomegalovirus belongs to the large group of 'private' genes that show no homology to those of other cytomegalovirus species and are thought to represent 'host adaptation' genes involved in virus-host interaction. Previous interest in the m164 gene product was based on the presence of an immunodominant CD8 T-cell epitope presented at the surface of infected cells, despite interference by viral immune-evasion proteins. Here, we provide data to reveal that the m164 gene product shows unusual features in its cell biology. A novel strategy of mass-spectrometric analysis was employed to map the N terminus of the mature protein, 107 aa downstream of the start site of the predicted open reading frame. The resulting 36.5 kDa m164 gene product is identified here as an integral type-I membrane glycoprotein with exceptional intracellular trafficking dynamics, moving within the endoplasmic reticulum (ER) and outer nuclear membrane with an outstandingly high lateral membrane motility, actually 100 times higher than those published for cellular ER-resident proteins. Notably, gp36.5/m164 does not contain any typical ER-retention/retrieval signals, such as the C-terminal motifs KKXX or KXKXX, and does not pass the Golgi apparatus. Instead, it belongs to the rare group of viral glycoproteins in which the transmembrane domain (TMD) itself mediates direct ER retention. This is the first report relating TMD usage of an ER-resident transmembrane protein to its lateral membrane motility as a paradigm in cell biology. We propose that TMD usage for ER retention facilitates free and fast floating in ER-related membranes and between ER subdomains.
鼠巨细胞病毒的基因 m164 属于“私有”基因的大组，与其他巨细胞病毒物种没有同源性，被认为是代表病毒-宿主相互作用中“宿主适应”的基因。先前对 m164 基因产物的兴趣基于存在免疫显性 CD8 T 细胞表位，尽管受到病毒免疫逃逸蛋白的干扰，但该表位在感染细胞的表面呈现。在这里，我们提供的数据揭示了 m164 基因产物在其细胞生物学中具有不寻常的特征。采用了一种新的质谱分析策略来绘制成熟蛋白的 N 末端，该蛋白位于预测开放阅读框起始位点的下游 107 个氨基酸处。由此产生的 36.5 kDa m164 基因产物被鉴定为一种独特的 I 型膜糖蛋白，具有异常的细胞内运输动力学，在内质网 (ER) 和外核膜内移动，具有极高的侧向膜运动性，实际上比已发表的细胞 ER 驻留蛋白高 100 倍。值得注意的是，gp36.5/m164 不包含任何典型的 ER 保留/检索信号，例如 C 末端基序 KKXX 或 KXKXX，也不通过高尔基体。相反，它属于罕见的病毒糖蛋白组之一，其中跨膜结构域 (TMD) 本身介导直接 ER 保留。这是第一个将 ER 驻留跨膜蛋白的 TMD 用途与其作为细胞生物学范例的侧向膜运动性相关联的报告。我们提出，用于 ER 保留的 TMD 用途促进了 ER 相关膜和 ER 亚区之间的自由和快速浮动。
