The structure and oligomerization of the yeast arginine methyltransferase,Hmt1

Protein methylation at arginines is ubiquitous in eukaryotes and affects si gnal transduction. gene expression and protein sorting. Hmt1/Rmt1, the majo r arginine methyltransferase in yeast, catalyzes methylation of arginine re sidues in several mRNA-binding proteins and facilitates their export from t he nucleus. We now report the crystal structure of Hmt1 at 2.9 Angstrom res olution. Hmt1 forms a hexamer with approximate 32 symmetry. The surface of the oligomer is dominated by large acidic cavities at the dimer interfaces. Mutation of dimer contact sites eliminates activity of Hmt1 both in vivo a nd in vitro. Mutating residues in the acidic cavity significantly reduces b inding and methylation of the substrate Np13.