Abstract of the PDB Structure's related Publication:
RNA methyltransferases (MTases) are important players in the biogenesis and regulation of the ribosome, the cellular machine for protein synthesis. RsmC is a MTase that catalyzes the transfer of a methyl group from S-adenosyl-l-methionine (SAM) to G1207 of 16S rRNA. Mutations of G1207 have dominant lethal phenotypes in Escherichia coli, underscoring the significance of this modified nucleotide for ribosome function. Here we report the crystal structure of E. coli RsmC refined to 2.1 A resolution, which reveals two homologous domains tandemly duplicated within a single polypeptide. We characterized the function of the individual domains and identified key residues involved in binding of rRNA and SAM, and in catalysis. We also discovered that one of the domains is important for the folding of the other. Domain duplication and subfunctionalization by complementary degeneration of redundant functions (in particular substrate binding versus catalysis) has been reported for many enzymes, including those involved in RNA metabolism. Thus, RsmC can be regarded as a model system for functional streamlining of domains accompanied by the development of dependencies concerning folding and stability.
RsmC catalyzes the transfer of a methyl group from S-adenosyl-l-methionine (SAM) to G1207 in hairpin 34 of 16S rRNA (m2G1207). It has two homologous domains tandemly duplicated within a single polypeptide. The enzyme reacts well with 30S subunits reconstituted from 16S RNA transcripts and 30S proteins, but is almost inactive with the corresponding free RNA. E. coli RsmC is closely related to E. coli RsmD (m2G966/16S rRNA) and also to a family of other MTases from Gram-positive bacteria and Archaea, typified by the Mj0882 protein from M. jannaschii (1dus in PDB) (The acronym RsmC has also been used for for ‘Regulator of Secondary Metabolism C’, a protein not related to Ribosomal small subunit Methyltransferase C).
Phylogenomic analysis of 16S rRNA:(guanine-N2) methyltransferases suggests new family members and reveals highly conserved motifs and a domain structure similar to other nucleic acid amino-methyltransferases.
RNA:(guanine-N2) methyltransferases RsmC/RsmD and their homologs revisited--bioinformatic analysis and prediction of the active site based on the uncharacterized Mj0882 protein structure.