Potassium viroporins as model systems for understanding eukaryotic ion channel behaviour

Abstract

Ion channels are membrane proteins essential for a plethora of cellular functions including maintaining cell shape, ion homeostasis, cardiac rhythm and action potential in neurons. The complexity and often extensive structure of eukaryotic membrane proteins makes it difficult to understand their basic biological regulation. Therefore, this article suggests, viroporins - the miniature versions of eukaryotic protein homologs from viruses - might serve as model systems to provide insights into behaviour of eukaryotic ion channels in general. The structural requirements for correct assembly of the channel along with the basic functional properties of a K⁺ channel exist in the minimal design of the viral K⁺ channels from two viruses, Chlorella virus (Kcv) and Ectocarpus siliculosus virus (Kesv). These small viral proteins readily assemble into tetramers and they sort in cells to distinct target membranes. When these viruses-encoded channels are expressed into the mammalian cells, they utilise their protein machinery and hence can serve as excellent tools to study the cells protein sorting machinery. This combination of small size and robust function makes viral K⁺ channels a valuable model system for detection of basic structure-function correlations. It is believed that molecular and physiochemical analyses of these viroporins may serve as basis for the development of inhibitors or modulators to ion channel activity for targeting ion channel diseases - so called channelopathies. Therefore, it may provide a potential different scope for molecular pharmacology studies aiming at novel and innovative therapeutics associated with channel related diseases. This article reviews the structural and functional properties of Kcv and Kesv upon expression in mammalian cells and Xenopus oocytes. The mechanisms behind differential protein sorting in Kcv and Kesv are also thoroughly discussed.

Keywords: Channelopathies; Ion channel; K(+) channels; Kcv; Kesv; Protein sorting; Viroporins.