Abstract:
:Lysine methyltransferases (KMTs) were initially associated with transcriptional control through their methylation of histones and other nuclear proteins, but have since been found 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. AKMT dimerizes via a unique intermolecular interface mediated by the C-terminal 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 parasite egress from infected host cells in vivo. Structural comparisons reveal that AKMT is related to the KMTs in the SMYD family, with, however, a number of distinct structural features in addition to the unusual dimerization interface. These features are conserved among the apicomplexan parasites and their free-living relatives, but not found in any known KMTs in animals. AKMT therefore is the founding member of a new subclass of KMT that has important implications for the evolution of the apicomplexans.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Pivovarova Y,Liu J,Lesigang J,Koldyka O,Rauschmeier R,Hu K,Dong Gdoi
10.1016/j.jmb.2018.08.017subject
Has Abstractpub_date
2018-10-19 00:00:00pages
4209-4229issue
21eissn
0022-2836issn
1089-8638pii
S0022-2836(18)30422-4journal_volume
430pub_type
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