Small viral channels as tools to understand sorting of membrane proteins

藻DNA病毒科（Phycodnaviridae）是一个大型双链DNA病毒家族。系统发育分析表明，它们的蛋白质可能是原核生物和真核生物中蛋白质同源物的进化起源。在几种小球藻病毒中发现了K+通道（Kcv）基因后，我们现在发现了另一种藻DNA病毒，即远亲的Ectocarpus病毒（EsV-1），它编码K+通道（Kev）。值得注意的是，这两个通道，尽管在结构上相似，但被分选到不同的靶膜。当Kcv通过分泌途径到达质膜时，Kev被分选到线粒体。由于它们的小尺寸，这两个通道提供了一个强大的系统，以改善我们对ER/线粒体靶向膜蛋白的分选信号的不完全理解。作为内部靶向信号的一个强有力的候选者是通道的第二跨膜结构域（TM 2）的结构;在Kev中TM 2的延伸足以将分选从线粒体切换到分泌途径。进一步的实验将利用通道之间的突变、缺失和结构域交换来鉴定靶向信号和机制。进一步的实验将检查Kev插入线粒体内膜的功能及其在EsV-1溶原性生命周期中的病理生理学相关性。

The Phycodnaviridae are a family of large dsDNA viruses. Phylogenetic analysis suggests that their proteins might be the evolutionary origin of protein homologs in pro- and eukaryotes. After finding a gene for a K+ channel (Kcv) in several Chlorella viruses we have now found another Phycodnavirus, the distantly related Ectocarpus virus (EsV-1), which encodes a K+ channel (Kev). Remarkable is that both channels, albeit similar in structure, are sorted to different target membranes. While Kcv reaches the plasma membrane via the secretory pathway, Kev is sorted to the mitochondria. Because of their small size the two channels offer a powerful system to improve our incomplete understanding of sorting signals for ER/mitochondria targeting of membrane proteins. A strong candidate as internal targeting signal is the architecture of the second transmembrane domain (TM2) of the channels; extension of TM2 in Kev is sufficient to switch sorting from the mitochondria to the secretory pathway. Further experiments will make use of mutations, deletions and domain swapping between the channels to identify the targeting signal(s) and mechanisms. Further experiments will examine the functional insertion of Kev into the inner mitochondrial membrane and its pathophysiological relevance in the lysogenic life cycle of EsV-1.