Lens β-crystallins: THE role of deamidation and related modifications in aging and cataract

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58 Scopus citations

Abstract

Crystallins are the major proteins in the lens of the eye and function to maintain transparency of the lens. Of the human crystallins, α, β, and γ, the β-crystallins remain the most elusive in their structural significance due to their greater number of subunits and possible oligomer formations. The β-crystallins are also heavily modified during aging. This review focuses on the functional significance of deamidation and the related modifications of racemization and isomerization, the major modifications in β-crystallins of the aged human lens. Elucidating the role of these modifications in cataract formation has been slow, because they are analytically among the most difficult post-translational modifications to study. Recent results suggest that many amides deamidate to similar extent in normal aged and cataractous lenses, while others may undergo greater deamidation in cataract. Mimicking deamidation at critical structural regions induces structural changes that disrupt the stability of the β-crystallins and lead to their aggregation invitro. Deamidations at the surface disrupt interactions with other crystallins. Additionally, the α-crystallin chaperone is unable to completely prevent deamidated β-crystallins from insolubilization. Therefore, deamidation of β-crystallins may enhance their precipitation and light scattering invivo contributing to cataract formation.Future experiments are needed to quantify differences in deamidation rates at all Asn and Gln residues within crystallins from aged and cataractous lenses, as well as racemization and isomerization which potentially perturb protein structure greater than deamidation alone. Quantitative data is greatly needed to investigate the importance of these major age-related modifications in cataract formation.

Original languageEnglish (US)
Pages (from-to)21-31
Number of pages11
JournalProgress in Biophysics and Molecular Biology
Volume115
Issue number1
DOIs
StatePublished - Jul 2014

Keywords

  • Aging
  • Beta-crystallins
  • Cataracts
  • Deamidation
  • Post-translational modification
  • Proteomics

ASJC Scopus subject areas

  • Biophysics
  • Molecular Biology

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