Work

Age‐dependent modification of proteins: N‐terminal racemization

Year: 2013

Type: article

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.

Source: FEBS Journal

DOI: 10.1111/febs.12217

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

Institutions: The University of Sydney, Macquarie University, University of Wollongong, Illawarra Health and Medical Research Institute

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: bronze

Funders: National Health and Medical Research Council, National Medical Research Council

Award: What causes human cataract?