Isomerization as the secret Achilles' heel of long-lived proteins

  1. Angela M. Gronenborn1
  1. From the Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213
  1. ?1 To whom correspondence should be addressed. E-mail: amg100{at}pitt.edu.
  1. Edited by Ursula Jakob

Abstract

Crystallin proteins, the dominant constituents of the eye lens, are prototypes of long-lived proteins. Such proteins can accumulate harmful modifications over their life span that render them prone to aggregation, which, in the case of lens crystallin, contributes to cataract formation. Lyon et al. now explore the structural and functional consequences of amino acid isomerization in α-crystallins using mass spectrometry, molecular dynamics simulations, and other strategies. Their results highlight the potential deleterious effects of these under-detected modifications on protein structural integrity and function.

Footnotes

  • Work in the authors' laboratory is supported by National Institutes of Health Grants GM082251 and DK114855 and National Science Foundation Grant CHE-1708773. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.

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