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

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

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1
Save Sight Institute, University of Sydney, Sydney Eye Hospital, NSW, Australia.

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.

PMID:
23448273
DOI:
10.1111/febs.12217
[Indexed for MEDLINE]
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