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Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
Published on: May 18, 2017
Age-dependent modification of proteins: N-terminal racemization
Brian Lyons1, Ann H Kwan, Joanne Jamie
1Save Sight Institute, University of Sydney, Sydney Eye Hospital, NSW, Australia.
The FEBS Journal
|March 2, 2013
Summary
Protein racemization, the aging process where amino acids change shape, occurs even at body temperature. This age-dependent protein deterioration affects human health and may contribute to age-related diseases.
Area of Science:
- Biochemistry
- Protein Chemistry
- Aging Research
Background:
- Long-lived proteins undergo age-dependent deterioration, impacting health and disease in the elderly.
- This denaturation is partly due to the intrinsic instability of certain amino acids, but the exact mechanisms remain unclear.
Purpose of the Study:
- To investigate age-dependent amino acid reactions in proteins.
- To understand the mechanisms of protein denaturation and racemization.
Main Methods:
- Incubation of peptides (PFHSPSY) at physiological pH and elevated temperatures.
- Nuclear Magnetic Resonance (NMR) spectroscopy to identify peptide products.
- Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) to analyze racemization in long-lived proteins.
Main Results:
- Incubation of a peptide from human αB-crystallin resulted in N-terminal proline (Pro) racemization.
- N-terminal racemization was observed in peptides with N-terminal Ser and Ala residues.
- Approximately one-third of N-terminal methionine (Met) in aquaporin 0 from aged human lenses showed racemization at 37 °C.
Conclusions:
- N-terminal amino acid racemization is a significant age-dependent modification occurring at physiological temperatures.
- This racemization affects long-lived proteins like aquaporin 0 in aged human lenses.
- Understanding protein racemization is crucial for comprehending age-related health issues and diseases.
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