Abstract
Lysine methyltransferases (KMTs) were initially associated with transcriptional control through their methylation of histones and other nuclear proteins, but have since been shown to regulate many other cellular activities. The apical complex lysine (K) methyltransferase (AKMT) of the human parasite Toxoplasma gondii was recently shown to play a critical role in regulating cellular motility. Here we report a 2.1-Å resolution crystal structure of the conserved and functional C-terminal portion (aa289-709) of T. gondii AKMT. Dimers of AKMT were observed to form via a unique intermolecular interface mediated by the C-terminal TPR (tetratricopeptide repeat)-like domain together with a specific zinc-binding motif that is absent from all other KMTs. Disruption of AKMT dimerization impaired both its enzyme activity and egress from infected host cells in vivo. Overall, our findings reveal AKMT as the founding member of a new subclass of KMTs that adopt a novel dimeric conformation to regulate cell motility.