Age-dependent modification of proteins: N-terminal racemization

FEBS J. 2013 May;280(9):1980-90. doi: 10.1111/febs.12217. Epub 2013 Mar 20.


Age-dependent deterioration of long-lived proteins in humans may have wide-ranging effects on health, fitness and diseases of the elderly. To a large extent, denaturation of old proteins appears to result from the intrinsic instability of certain amino acids; however, these reactions are incompletely understood. One method to investigate these reactions involves exposing peptides to elevated temperatures at physiological pH. Incubation of PFHSPSY, which corresponds to a region of human αB-crystallin that is susceptible to age-related modification, resulted in the appearance of a major product. NMR spectroscopy confirmed that this novel peptide formed via racemization of the N-terminal Pro. This phenomenon was not confined to Pro, because peptides with N-terminal Ser and Ala residues also underwent racemization. As N-terminal racemization occurred at 37 °C, a long-lived protein was examined. LC-MS/MS analysis revealed that approximately one third of aquaporin 0 polypeptides in the centre of aged human lenses were racemized at the N-terminal methionine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Amino Acid Sequence
  • Aquaporins / chemistry*
  • Aquaporins / metabolism*
  • Eye Proteins / chemistry*
  • Eye Proteins / metabolism*
  • Humans
  • Isomerism
  • Lens, Crystalline / metabolism
  • Methionine / chemistry
  • Peptide Fragments / chemistry*
  • Proline / chemistry
  • Protein Stability
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Tandem Mass Spectrometry
  • alpha-Crystallin B Chain / chemistry*


  • Aquaporins
  • Eye Proteins
  • Peptide Fragments
  • alpha-Crystallin B Chain
  • aquaporin 0
  • Proline
  • Methionine