Small viral channels as tools to understand sorting of membrane proteins

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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.