Biochemistry and regulation of the protein arginine methyltransferases (PRMTs)

Arch Biochem Biophys. 2016 Jan 15;590:138-152. doi: 10.1016/j.abb.2015.11.030. Epub 2015 Dec 2.

Abstract

Many key cellular processes can be regulated by the seemingly simple addition of one, or two, methyl groups to arginine residues by the nine known mammalian protein arginine methyltransferases (PRMTs). The impact that arginine methylation has on cellular well-being is highlighted by the ever growing evidence linking PRMT dysregulation to disease states, which has marked the PRMTs as prominent pharmacological targets. This review is meant to orient the reader with respect to the structural features of the PRMTs that account for catalytic activity, as well as provide a framework for understanding how these enzymes are regulated. An overview of what we understand about substrate recognition and binding is provided. Control of product specificity and enzyme processivity are introduced as necessary but flexible features of the PRMTs. Precise control of PRMT activity is a critical component to eukaryotic cell health, especially given that an arginine demethylase has not been identified. We therefore conclude the review with a comprehensive discussion of how protein arginine methylation is regulated.

Keywords: Arginine methylation; Dimethylarginine; Monomethylarginine; PRMT; Protein arginine methyltransferase; S-adenosyl methionine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arginine / chemistry*
  • Arginine / metabolism*
  • Binding Sites
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic / physiology*
  • Humans
  • Methylation
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Protein-Arginine N-Methyltransferases / chemistry*
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Protein-Arginine N-Methyltransferases / ultrastructure
  • Substrate Specificity

Substances

  • Arginine
  • Protein-Arginine N-Methyltransferases