Referenced in: none

Automatically associated channels: Kir2.3

Title: Age-dependent modification of proteins: N-terminal racemization.

Authors: Brian Lyons, Ann H Kwan, Joanne Jamie, Roger J W Truscott

Journal, date & volume: FEBS J., 2013 May , 280, 1980-90

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23448273

Abstract
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.