遗传性珊瑚状白内障突变晶状体蛋白分子构型及超微结构分析

Ultrastructure and crystallinmutant molecular modeling of hereditary coralliform cataract

目的:探讨珊瑚状遗传性白内障家系P23T突变的γD晶状体蛋白与病变晶状体结构的关系。方法:记录晶状体摘除术前的晶状体裂隙灯照片;应用SWISS-MODEL程序,建立人γD晶状体蛋白及其P23T突变体的计算机立体结构模型;透射和扫描电镜观测晶状体提取物。结果:蛋白立体结构模型分析发现,P23T的突变降低了蛋白最终分子总势能,使蛋白表面结构发生改变。电镜检查发现,白内障晶状体内有大小不等的结晶片和异常的卵圆形结构,晶状体上皮细胞出现裂解。结论:γD晶状体蛋白P23T突变体可能与晶状体内异常结晶片和晶状体上皮细胞的病理改变有关,其发生机制还有待分子动力学的研究。

Objective: To observe the correlation ofγD crystallin P23T mutant with lens ultrastructure of the hereditary coralliform cataract. Methods: Complete ophthalmologic examinations were performed before lens extraction and lens samples were studied by transmission and scanning electric microscope respectively.Protein molecular modeling was performed using SWISS MODEL(version 2.0). Results: Protein structuremodeling demonstrated that the mutant caused a decrease in molecular final total energy and changes in the surface structure of γD crystallin.Ultrastructurestudy revealed crystals deposited in lens,extensive granules dispersed in uncommon oval structure and the disorganization of lens epithelial cells. Conclusion: It is possible that the γD crystallin P23T mutant is associated with abnormal crystals in lens and disorganization of lens epithelial cells.