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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Cataract mutation P20S of alpha beta-crystallin impairs chaperone activity of alpha A-crystallin and induces apoptosis of human lens epithelial cells
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Cataract mutation P20S of alpha beta-crystallin impairs chaperone activity of alpha A-crystallin and induces apoptosis of human lens epithelial cells

机译：α-β-晶状体蛋白的白内障突变P20S损害α-A-晶状体蛋白的伴侣活性并诱导人晶状体上皮细胞凋亡

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摘要

Cataract is a common cause of childhood blindness worldwide. a-crystallin, which is comprised of two homologous subunits, alpha A- and alpha B-crystallin, plays a key role in the maintenance of lens transparency. Recently, we have identified a missense mutation in alpha beta-crystallin that changes the proline residue at codon 20 to a serine residue (P20S) in a large Chinese family with autosomal dominant posterior polar congenital cataract. To explore the molecular mechanism by which the P20S mutation causes cataract, we examined the quaternary structure, subunit exchange and chaperone activity of the reconstituted heteroaggregates of alpha-crystallins containing wild type (WT) alpha A in combination with either WT-alpha B- or mutant alpha B-crystallin, respectively. Compared with heteroaggregates of WT-alpha A and WT-alpha B, heteroaggregates containing WT-alpha A and mutant alpha B showed nearly the same molecular mass, but the subunit-exchange rate and chaperone activity were decreased markedly. In human lens epithelial cells, unlike WT-alpha B-crystallin, the P20S mutant protein showed abnormal nuclear localization, and unusual ability to trigger apoptosis. These results suggest that the changes in the structure and function of the a-crystallin complex and cytotoxicity are vital factors in the pathogenesis of congenital cataract linked to the P20S mutation in the alpha B-crystallin. (c) 2008 Elsevier B.V. All rights reserved.
机译：白内障是全世界儿童失明的常见原因。 α-晶状蛋白由两个同源的亚基α-A和晶状体B-晶状蛋白组成，在维持晶状体透明性方面起着关键作用。最近，我们发现了一个常染色体显性后极先天性白内障的中国大家庭，αβ-晶状蛋白的错义突变将20位密码子的脯氨酸残基变为丝氨酸残基（P20S）。为了探索P20S突变引起白内障的分子机制，我们研究了含有野生型（WT）αA与WT-alpha B-或野生型（WT）alpha A的重组α-晶状蛋白的杂聚集体的四级结构，亚基交换和分子伴侣活性。突变体αB-crystallin分别。与WT-alpha A和WT-alpha B的杂聚体相比，包含WT-alpha A和突变体αB的杂聚体显示出几乎相同的分子量，但亚基交换率和伴侣活性显着降低。在人晶状体上皮细胞中，与WT-alpha B-crystallin不同，P20S突变蛋白显示出异常的核定位，并具有异常的触发细胞凋亡的能力。这些结果表明，a-晶状体蛋白复合物的结构和功能以及细胞毒性的变化是与αB-晶状体蛋白的P20S突变有关的先天性白内障发病机理中的重要因素。 （c）2008 Elsevier B.V.保留所有权利。

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