Lens β-crystallins: the role of deamidation and related modifications in aging and cataract.
Lens β-crystallins: the role of deamidation and related modifications in aging and cataract.
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DOI：
10.1016/j.pbiomolbio.2014.02.004
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发表时间：
2014-07
影响因子：
3.8
通讯作者：
David LL
中科院分区：
文献类型：
--
作者：
Lampi KJ;Wilmarth PA;Murray MR;David LL
晶体蛋白是晶状体中的主要蛋白质，其作用是维持晶状体的透明度。在人类晶体蛋白α、β和γ中，β-晶体蛋白由于其大量的亚基和可能的低聚物形成，其结构意义仍然是最难以捉摸的。β-结晶蛋白在衰老过程中也会发生很大的变化。本文综述了老化晶状体β-晶体蛋白的脱酰胺化及其相关的外消旋化和异构化修饰的功能意义。阐明这些修饰在白内障形成中的作用一直很缓慢，因为它们在分析上是最难研究的翻译后修饰之一。最近的研究结果表明，许多酰胺在正常年龄和白内障晶体中脱酰胺程度相似，而其他酰胺在白内障中可能经历更大的脱酰胺。在关键结构区域模拟脱酰胺诱导结构变化，破坏β-结晶蛋白的稳定性并导致它们在体外聚集。表面的脱酰胺破坏了与其他晶体蛋白的相互作用。此外，α-晶体蛋白伴侣不能完全阻止脱酰胺β-晶体蛋白的不溶化。因此，β-晶体蛋白的脱酰胺可能会增强其在体内的沉淀和光散射，从而促进白内障的形成。未来的实验需要量化老化和白内障晶状体晶体蛋白中所有Asn和Gln残基脱酰胺率的差异，以及外消旋化和异构化，它们可能比单独脱酰胺更能扰乱蛋白质结构。定量数据是非常必要的，以调查这些主要的年龄相关的改变在白内障形成中的重要性。
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 in vitro. 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 in vivo 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.
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DOI：
10.1074/mcp.m113.034769
发表时间：
2014-01
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Hebert AS;Richards AL;Bailey DJ;Ulbrich A;Coughlin EE;Westphall MS;Coon JJ
通讯作者：
Coon JJ
影响因子：
7.4
作者：
Abzalimov, Rinat R.;Bobst, Cedric E.;Kaltashov, Igor A.
通讯作者：
Kaltashov, Igor A.
影响因子：
4.4
作者：
Hains, Peter G.;Truscott, Roger J. W.
通讯作者：
Truscott, Roger J. W.
影响因子：
3.4
作者：
Hanson, SRA;Hasan, A;Smith, JB
通讯作者：
Smith, JB
影响因子：
17.8
作者：
Carver, JA
通讯作者：
Carver, JA