Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, China.
Biol Chem. 2010 Dec;391(12):1391-400. doi: 10.1515/BC.2010.143.
αB-Crystallin plays an important part in cataract development. A novel mutation (R11H) was previously detected by our group. In the present study, we set out to investigate the possible molecular mechanism by which the R11H mutation causes cataract. We found that the mutant αB-crystallin exhibits folding defects, decreased surface hydrophobicity and enhanced chaperone-like activity compared with the wild-type αB-crystallin. The mutant protein shows nearly the same molecular mass and thermal stability as the wild-type form. Transfection studies revealed that the R11H mutant was remarkably similar to the wild-type protein in its subcellular distribution, but has an abnormal ability to induce cell apoptosis. These results suggest that the changes in hydrophobic exposure and the abnormal ability to induce programmed cell death of the mutant protein are likely to be responsible for the onset of cataract.
αB-晶状体蛋白在白内障的发生发展中起着重要作用。我们小组先前检测到一种新型突变（R11H）。在本研究中，我们着手研究 R11H 突变导致白内障的可能分子机制。我们发现，与野生型 αB-晶状体蛋白相比，突变型 αB-晶状体蛋白表现出折叠缺陷、表面疏水性降低和增强的分子伴侣样活性。突变蛋白的分子量和热稳定性与野生型相似。转染研究表明，突变体在亚细胞分布上与野生型蛋白非常相似，但诱导细胞凋亡的能力异常。这些结果表明，突变蛋白的疏水性暴露改变和诱导程序性细胞死亡的异常能力可能是白内障发生的原因。
