Arginine and lysine methylproteomes of Giardia duodenalis

ABSTRACT: Methylation is a common post-translational modification of lysine and arginine in eukaryotic proteins. To date, these methylomes are best characterised in model organisms and higher eukaryotes. Herein, we integrated bioinformatics, proteomics and high-content drug-screening to comprehensively explore protein methylation in the human gastrointestinal parasite and deep-branching eukaryote, Giardia duodenalis. We demonstrate Giardia and other Diplomonadida species lack arginine-methyltransferases and have remodelled RGG/RG motifs preferred by these enzymes. Further, Giardia had no detectable methylarginine in vitro, demonstrating the first eukaryote with no arginine methylome. In contrast, we performed detailed curation of 11 putative lysine-methyltransferases, including highly-diverged SET-domain proteins, and novel annotations demonstrating conserved eEF1a methyllysine. We identified >200 high-confidence methyllysine sites, highlighting methyllysine within coiled-coil features, and for Giardia cytoskeletal regulation. Lastly, using known methylation-inhibitors, we demonstrate inhibition of methylation plays a key role in replication and cyst formation in this parasite.

OTHER RELATED OMICS DATASETS IN: MODEL1109130000 MODEL1909260003 MODEL1909260004 MODEL1703310000 MODEL1909260005 MODEL1909260006 MODEL1311110000 MODEL1311110001

INSTRUMENT(S):

ORGANISM(S): Giardia Lamblia Atcc 50803

TISSUE(S): Trophozoite, Binucleate Cell

DISEASE(S): Giardiasis

SUBMITTER: Samantha Emery  

LAB HEAD: Aaron R Jex

PROVIDER: PXD016813 | Pride | 2020-08-07

REPOSITORIES: pride