Age‐dependent modification of proteins: N‐terminal racemization. (20th March 2013)

• Record Type: Journal Article
• Authors: Lyons, Brian; Kwan, Ann H.; Jamie, Joanne; Truscott, Roger J. W.
• Is Part Of: FEBS journal. Volume 280:Number 9(2013)
• Page Start: 1980
• Page End: 1990
• Publication Date: 2013-03-20
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.12217
• Languages: English
• ISSNs: 1742-464X

Abstract

<abstract abstract-type="main" id="febs12217-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="febs12217-sec-0001" sec-type="section"> <p>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<bold>‐</bold>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<bold>‐</bold>terminal Pro. This phenomenon was not confined to Pro, because peptides with N<bold>‐</bold>terminal Ser and Ala residues also underwent racemization. As N<bold>‐</bold>terminal racemization occurred at 37 °C, a long‐lived protein was examined. LC<bold>‐</bold>MS/MS analysis revealed that approximately one third of aquaporin 0 polypeptides in the centre of aged human lenses were racemized at the N<bold>‐</bold>terminal methionine.</p> </sec> <sec id="febs12217-sec-0002" sec-type="section"> <title>Structured digital abstract</title> <p> LAP cleaves AQP0 by enzymatic study (View interaction).</p> </sec> </abstract>