K+ channels play a vital homeostatic role in cells and abnormal activity of these channels can dramatically alter cell function and survival suggesting that they might be attractive drug targets in pathogenic organisms. Differences in the sequences and diversity of human and parasite proteins may allow GR 38032F pathogen-specific targeting of these K+ channel homologues. Introduction Protozoan parasites are major contributors to worldwide disease [1]. They include apicomplexan parasites such as spp. (malaria) (toxoplasmosis) spp. (cryptosporidiosis diarrhoea) and (babesiosis) as well as the kinetoplastid parasites spp. (sleeping sickness Chagas’ disease) and spp. (leishmaniasis). These parasites are together responsible for billions of infections and hundreds of thousands of deaths each year [1] [2]. Other protozoan parasites causing widespread disease include (giardiasis) (dysentery) and (trichomoniasis). Current treatments for diseases caused by protozoa are often ineffective or poorly tolerated and emergence of drug resistance is an imminent threat to their efficacy [3]–[5]. New therapeutic targets and drugs are therefore needed. K+ channels are a diverse family of transmembrane proteins which form K+-selective pores and mediate K+ flux across membranes [6] [7]. K+ channels are essential components in a multitude of homeostatic and signalling pathways and are present in animal cells [6] plants [8] [9] fungi [10] [11] and many bacteria [7] [12]. Only a handful of L1CAM organisms appear to lack K+ channels completely and most of these are bacteria that are obligate parasites [7] [12]. Many K+ channels are present in free-living protozoa such as spp. [14]–[16] and K+-conductive pathways have also been observed in and is lethal to these parasites [16] [37]. Recent advances in genomics have resulted in whole-genome sequencing of many pathogenic protozoa [1] [38]–[56]. In this study we examine the genomes of pathogenic protozoa comprehensively using diverse K+ channel sequences from mammals plants fungi bacteria and archaea to search for the presence of predicted proteins that may fulfil roles as K+ channels. We show that genes encoding homologues of K+ channels exist in all pathogenic protozoa examined. Sequence divergence of putative protozoan channels from their human counterparts in regions that are known to be important for channel activation ion conduction or drug binding may result in distinct pharmacological GR 38032F profiles. These parasite channels may therefore represent novel targets for anti-parasitic therapy. Results Identification and classification of K+ channel homologues The defining feature of K+ channels is their selectivity for K+ ions which is conferred by residues within the selectivity filter region of the pore [57] (Figure 1). Diverse mammalian K+ channels show sequence similarity in the selectivity filter region with a core selectivity filter motif of XXGXGX most commonly TXGYGD [58]. K+ selectivity is known to be tolerant of some sequence variation in this selectivity filter motif [59] as well as in the outer and inner pore regions and such variation exists between channel subtypes [58]. For example selectivity filter sequences of K+-selective channels include TIGYGF (Kir2.1 Kir2.3) TIGYGL (Kir2.2) XXGFGX (Kir6.2 ERG EAG mouse KCa1.1) and XXGLGD (some K2P) [58]. We therefore searched parasite genomes using diverse K+ channel sequences from humans plants fungi bacteria and archaea (see Methods) which together cover most known K+-selective pore sequences. We identified predicted protein products in the genomes of pathogenic protozoa which GR 38032F display significant sequence similarity to K+ channels in the pore region GR 38032F including the selectivity filter (Table 1 and Figure 2). These proteins also satisfy other criteria for defining them as putative K+ channel homologues such as the presence of multiple TMDs (see Methods). These homologues may therefore function as K+-selective channels in protozoan parasites. Homologues were classified according to the family of human K+ channel to which they showed greatest sequence similarity and according to the presence of conserved functional domains (Figure 1A) such as putative voltage sensors Ca2+-sensing regulator of conductance (RCK) domains of KCa channels [60]–[63] calmodulin (CaM)-binding domains (CaMBDs) [60] [64] or cyclic nucleotide-binding domains (CNBDs) [65] (Table 1 and Figure 2). The proteins {“type”:”entrez-protein” attrs :{“text”:”XP_001609692″ term_id :”156084418″.