Temperature-dependent structural and functional properties of a mutant (F71L) αA-crystallin: molecular basis for early onset of age-related cataract.
Temperature-dependent structural and functional properties of a mutant (F71L) αA-crystallin: molecular basis for early onset of age-related cataract.
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突变体 (F71L) αA-晶状体蛋白的温度依赖性结构和功能特性：年龄相关性白内障早期发病的分子基础。
DOI：
10.1016/j.febslet.2011.10.049
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发表时间：
2011-12-15
期刊：
影响因子：
3.5
通讯作者：
Reddy GB
中科院分区：
文献类型：
--
作者：
Validandi V;Reddy VS;Srinivas PN;Mueller NH;Bhagyalaxmi SG;Padma T;Petrash JM;Reddy GB
Previously we identified a novel mutation (F71L) in the αA-crystallin gene associated with early onset of age-related cataract. However, it is not known how the missense substitution translates into reduced chaperone-like activity (CLA), and how the structural and functional changes lead to early onset of the disease. Herein, we show that under native conditions the F71L-mutant is not significantly different from wild-type with regard to secondary and tertiary structural organization, hydrophobicity and the apparent molecular mass of oligomer but has substantial differences in structural and functional properties following a heat treatment. Wild-type αA-crystallin demonstrated increased CLA, whereas the F71L-mutant substantially lost its CLA upon heat treatment. Further, unlike the wild-type αA-subunit, F71L-subunit did not protect the αB-subunit in hetero-oligomeric complex from heat-induced aggregation. Moreover, hetero-oligomer containing F71L and αB in 3:1 ratio had significantly lower CLA upon thermal treatment compared to its unheated control. These results indicate that α-crystallin complexes containing F71L-αA subunits are less stable and have reduced CLA. Therefore, F71L may lead to earlier onset of cataract due to interaction with several environmental factors (e.g., temperature in this case) along with the aging process.
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DOI：
10.1073/pnas.96.11.6137
发表时间：
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影响因子：
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