Molecular characterization of EhAK6, an endonuclease V domain-containing aurora kinase protein from Entamoeba histolytica: Protein-protein interaction, docking and functional aspect

Abstract

• Entamoeba histolytica genome encodes 7 aurora kinase protein homologs (EhAK1-7). • EhAK6 has a unique endonuclease V domain in C-terminal position. • mRNA expression of EhAK6 is increased upon UV-C irradiation. • EhAK6 may play a role in chromosome segregation and DNA repair of E. histolytica . • EhAK6 directly interacts with a Sir2 homolog, EhSir2a as predicted by STRING analysis. Entamoeba histolytica is responsible for amoebiasis in humans. Its atypical cell cycle events and unique stress defense mechanisms make it different from other protozoan parasites. Comparative homology search identified seven homologs of aurora kinases (EhAK1-7) in E. histolytica . Aurora kinases are well-known essential regulators of mitotic and meiotic cell division in eukaryotic organisms. EhAK6 contains a unique C-terminal endonuclease V domain, which is not reported in any other known aurora kinases. Endonuclease V domain-containing proteins are known to repair DNA in prokaryotes. Interestingly, we found that the mRNA expression of EhAK6 is increased upon UV-C irradiation in wild-type and also in the EhAK6 over-expressing transformants, in this primitive protozoan parasite. Several DNA repair proteins and EhSir2a, a Sir2 homolog known to be involved in regulating microtubular assembly were found to be the interactors of EhAK6 but not for the other aurora kinases in E. histolytica . We have predicted the theoretical model of EhAK6 and analyzed its interaction with the interactors by molecular docking. We propose that EhAK6, an aurora kinase homolog may be involved in DNA repair system in this human pathogen.