Deamidation and isoaspartate formation in proteins: Unwanted alterations or surreptitious signals?

  • Reissner K
  • Aswad D
  • 82

    Readers

    Mendeley users who have this article in their library.
  • 170

    Citations

    Citations of this article.

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.

Author-supplied keywords

  • Deamidation
  • Isoaspartate
  • Peptide bond
  • Protein damage
  • Protein methylation
  • Protein-L-isoaspartyl O-methyltransferase
  • S-adenosyl-L-methionine

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • K. J. Reissner

  • D. W. Aswad

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free