Arginyltransferase ATE1 catalyzes midchain arginylation of proteins at side chain carboxylates in vivo

Chem Biol. 2014 Mar 20;21(3):331-7. doi: 10.1016/j.chembiol.2013.12.017. Epub 2014 Feb 13.


Arginylation is an emerging posttranslational modification mediated by Arg-tRNA-protein-transferase (ATE1). It is believed that ATE1 links Arg solely to the N terminus of proteins, requiring prior proteolysis or action by Met-aminopeptidases to expose the arginylated site. Here, we tested the possibility of Arg linkage to midchain sites within intact protein targets and found that many proteins in vivo are modified on the side chains of Asp and Glu by unconventional chemistry that targets the carboxy rather than the amino groups at the target sites. Such arginylation appears to be functionally regulated, and it can be directly mediated by ATE1, in addition to the more conventional ATE1-mediated linkage of Arg to the N-terminal alpha amino group. This midchain arginylation implies an unconventional mechanism of ATE1 action that likely facilitates its major biological role.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacyltransferases / chemistry
  • Aminoacyltransferases / genetics
  • Aminoacyltransferases / metabolism*
  • Angiotensin II / analysis
  • Angiotensin II / chemistry
  • Angiotensin II / metabolism
  • Animals
  • Aspartic Acid / chemistry
  • Aspartic Acid / metabolism
  • Biocatalysis
  • Chromatography, High Pressure Liquid
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism
  • Humans
  • Mice
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Substrate Specificity


  • Recombinant Proteins
  • Angiotensin II
  • Aspartic Acid
  • Glutamic Acid
  • Aminoacyltransferases
  • arginyltransferase