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Age-dependent racemization of serine residues in a human chaperone protein

Authors

  • Michelle Y. S. Hooi,

    1. Save Sight Institute, Sydney Eye Hospital, University of Sydney, Sydney, New South Wales 2000, Australia
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  • Mark J. Raftery,

    1. Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, New South Wales 2052, Australia
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  • Roger J. W. Truscott

    Corresponding author
    1. Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales 2522, Australia
    • Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia
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Abstract

Racemization is one of the most abundant modifications in long-lived proteins. It has been proposed that the accumulation of such modifications over time could lead to changes in tissues and ultimately human age-related diseases. Serine is one of the main amino acids involved in racemization; however, the site of D-Ser in any aged protein has yet to be reported. In this study, racemization of two residues, Ser 59 and Ser 62, has been demonstrated in an unstructured region of the small heat shock protein, αA-crystallin. αA-crystallin is also the most abundant structural protein in the human lens. D-Ser increased linearly with age in normal lenses, until it accounted for approximately 35% of the Ser at both sites by the age of 75 years. In agreement with a possible role in human age-related disease, levels were significantly higher in cataract lenses. It is likely that such prevalent age-related changes contribute to the denaturation of α-crystallin, and therefore its ability to act as a chaperone. Racemization of amino acids, such as serine, in flexible regions of long-lived proteins, could be associated with the development of human age-related conditions such as cataract.

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