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. 2019 May 10;294(19):7556-7557.
doi: 10.1074/jbc.H119.008716.

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

Alex J Guseman  1 , Angela M Gronenborn  2
Affiliations

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

Alex J Guseman et al. J Biol Chem. .

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.

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Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article

Figures

Figure 1.
Figure 1.
A, structure of the αB-crystallin dimer (PDB code 2KLR) and a model of the assembled 24-mer (PDB code 3J07). B, isomerization of Asp-109, one of the modifications explored by Lyon et al. (3), at the oligomer interface inhibits assembly into the functional quaternary structure.
See this image and copyright information in PMC

Comment in

References

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