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The ribosome: A hot spot for the identification of new types of protein methyltransferases - PubMed

  • ️Mon Jan 01 2018

The ribosome: A hot spot for the identification of new types of protein methyltransferases

Steven G Clarke. J Biol Chem. 2018.

Abstract

Cellular physiology depends on the alteration of protein structures by covalent modification reactions. Using a combination of bioinformatic, genetic, biochemical, and mass spectrometric approaches, it has been possible to probe ribosomal proteins from the yeast Saccharomyces cerevisiae for post-translationally methylated amino acid residues and for the enzymes that catalyze these modifications. These efforts have resulted in the identification and characterization of the first protein histidine methyltransferase, the first N-terminal protein methyltransferase, two unusual types of protein arginine methyltransferases, and a new type of cysteine methylation. Two of these enzymes may modify their substrates during ribosomal assembly because the final methylated histidine and arginine residues are buried deep within the ribosome with contacts only with RNA. Two of these modifications occur broadly in eukaryotes, including humans, whereas the others demonstrate a more limited phylogenetic range. Analysis of strains where the methyltransferase genes are deleted has given insight into the physiological roles of these modifications. These reactions described here add diversity to the modifications that generate the typical methylated lysine and arginine residues previously described in histones and other proteins.

Keywords: post-translational modification (PTM); protein methylation; protein methyltransferase; ribosome; ribosome structure; translation elongation factor.

© 2018 Clarke.

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Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article

Figures

Figure 1.
Figure 1.

Structures and nomenclature of selected “less traveled” methylated amino acid residues. The replacement of a hydrogen atom with a methyl group not only increases the steric bulk at that position in the peptide but also decreases the nucleophilicity of the linked nitrogen or sulfur atom. Methylation can also provide additional carbon-based hydrogen bond donors (25, 26). These bonds can form when the carbon atom of the methyl group is bonded to a nitrogen atom bearing a net positive charge, as with the proline, histidine, and arginine methylated derivatives shown in the figure.

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