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On “Isomerization as the secret Achilles’ heel of long-lived proteins”

  • Allen Taylor
    Correspondence
    To whom correspondence should be addressed: Director of the Laboratory for Nutrition and Vision Research, Professor of Nutrition, Development, Molecular and Chemical Biology, and Ophthalmology, USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington St., Boston, Massachusetts 02111. Tel.: 617-556-3156; Fax: 617-556-3132
    Affiliations
    Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging and Departments of Nutrition, Development, Molecular and Chemical Biology, and Ophthalmology, Tufts University, Boston, Massachusetts 02111
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Open AccessPublished:June 21, 2019DOI:https://doi.org/10.1074/jbc.L119.009476
      This summary (
      • Guseman A.J.
      • Gronenborn A.M.
      Isomerization as the secret Achilles' heel of long-lived proteins.
      ) calls to our attention the importance of often-overlooked stochastic processes that occur as proteins age—especially long-lived proteins. The demonstration by Lyon et al. (
      • Lyon Y.A.
      • Collier M.P.
      • Riggs D.L.
      • Degiacomi M.T.
      • Benesch J.L.P.
      • Julian R.R.
      Structural and functional consequences of age-related isomerization in α-crystallins.
      ) of the failed chaperone function of α-crystallins and its relationship to cataract and potentially other protein precipitation diseases is elegant. They should, however, acknowledge that Groenen et al. (
      • Groenen P.J.
      • van Dongen M.J.
      • Voorter C.E.
      • Bloemendal H.
      • de Jong W.W.
      Age-dependent deamidation of alpha B-crystallin.
      ) and Voorter et al. (
      • Voorter C.E.
      • de Haard-Hoekman W.A.
      • van den Oetelaar P.J.
      • Bloemendal H.
      • de Jong W.W.
      Spontaneous peptide bond cleavage in aging α-crystallin through a succinimide intermediate.
      ) published on this topic decades ago. Goenen showed how simple water-based hydrolysis after racemization can lead to the extensive cleavages that are observed in the aged lens.

      References

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        Isomerization as the secret Achilles' heel of long-lived proteins.
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        Structural and functional consequences of age-related isomerization in α-crystallins.
        J. Biol. Chem. 2019; 294 (30804217): 7546-7555
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        Age-dependent deamidation of alpha B-crystallin.
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        Spontaneous peptide bond cleavage in aging α-crystallin through a succinimide intermediate.
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