Journal
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
Volume 115, Issue 1, Pages 21-31Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbiomolbio.2014.02.004
Keywords
Beta-crystallins; Deamidation; Proteomics; Cataracts; Aging; Post-translational modification
Categories
Funding
- NIH [RO1 EY012239, RO1 EY007755, P30 EY010572]
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Crystallins are the major proteins in the lens of the eye and function to maintain transparency of the lens. Of the human crystallins, alpha, beta, and gamma, the beta-crystallins remain the most elusive in their structural significance due to their greater number of subunits and possible oligomer formations. The beta-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 beta-aystallins 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 beta-crystallins and lead to their aggregation in vitro. Deamidations at the surface disrupt interactions with other aystallins. Additionally, the a-crystallin chaperone is unable to completely prevent deamidated beta-crystallins from insolubilization. Therefore, deamidation of beta-crystallins may enhance their precipitation and light scattering in vivo contributing to cataract formation. Future experiments are needed to quantify differences in deamidation rates at all Asn and Gin 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. (C) 2014 Elsevier Ltd. All rights reserved.
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