Deamidation and Isoaspartate Formation in Proteins: Unwanted Alterations or Surreptitious Signals?

Cell Mol Life Sci. 2003 Jul;60(7):1281-95. doi: 10.1007/s00018-003-2287-5.

Abstract

Formation of betalinked Asp-Xaa peptide bonds--isoaspartyl (isoAsp) sites--arise in proteins via succinimide-linked deamidation of asparagine or dehydration of aspartate, reactions which represent a major source of spontaneous protein damage under physiological conditions. Accumulation of atypical isoaspartyl sites is minimized in vivo by the activity of protein L-isoaspartyl O-methyltransferase (PIMT), which regenerates a normal peptide bond. Loss of PIMT has harmful consequences, especially in neurons; thus, formation of isoAsp sites and their subsequent correction by PIMT is widely believed to constitute an important pathway of protein damage and repair. Recent evidence is mounting, however, that deamidation and isoaspartate formation may, in some instances, constitute a novel mechanism for intentional modification of protein structure. Herein we describe the mechanism of Asx rearrangement, summarize the evidence that PIMT serves an important repair function, and then focus on emerging evidence that deamidation and isoAsp formation may sometimes have a useful function.

Publication types

  • Review

MeSH terms

  • Amides / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Brain / enzymology
  • Escherichia coli / metabolism
  • Humans
  • Isoaspartic Acid / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase / chemistry
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase / genetics
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase / metabolism*
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / metabolism
  • Testis / enzymology

Substances

  • Amides
  • Isoaspartic Acid
  • Proteins
  • Ribosomal Proteins
  • ribosomal protein S1
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase