Age-dependent modification of proteins: N-terminal racemization

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

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages1980-1990
Number of pages11
JournalFEBS Journal
Volume280
Issue number9
DOIs
Publication statusPublished - May 2013

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Peptides
Proteins
Senior Centers
Protein Denaturation
Crystallins
Denaturation
Methionine
Lenses
Nuclear magnetic resonance spectroscopy
Deterioration
Magnetic Resonance Spectroscopy
Health
Amino Acids
Temperature
aquaporin 0

Cite this

Lyons, Brian ; Kwan, Ann H. ; Jamie, Joanne ; Truscott, Roger J W. / Age-dependent modification of proteins : N-terminal racemization. In: FEBS Journal. 2013 ; Vol. 280, No. 9. pp. 1980-1990.
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Age-dependent modification of proteins : N-terminal racemization. / Lyons, Brian; Kwan, Ann H.; Jamie, Joanne; Truscott, Roger J W.

In: FEBS Journal, Vol. 280, No. 9, 05.2013, p. 1980-1990.

Research output: Contribution to journalArticleResearchpeer-review

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