【摘要】 本研究前期工作发现在一个遗传性先天性白内障家系中,γD晶体蛋白发生了P23T突变.因此本研究对γD晶体蛋白及其突变体进行了氨基酸序列分析,结构域预测及立体结构模拟等生物信息学研究,以探讨P23T突变对γD晶体蛋白结构与功能的影响.研究结果表明:P23T突变可能影响人γD晶体蛋白与钙离子的结合,导致晶状体内钙离子动态失衡;可以使蛋白分子间形成氢键,降低晶体蛋白溶解度;并使蛋白质表面局部极性的改变,影响蛋白与其它分子的结合.更多还原

【Abstract】 A Pro-23→Thr (P23T) substitution in γD-crystallin protein was identified in a hereditary congenital cataract family through previous study. The amino acid sequence, protein domain and motifs, and three-dimension structure of γD-crystallin protein and its mutant were analyzed and predicted. The results showed that the mutation of γD-crystallin protein could affect the ability of the protein to bind itself with calcium ions, thereby inducing dynamic unbalance of the calcium ions in lens. The intermolecular hydrogen-bonds were rearranged, which would reduce the solubility of mutant γD protein. Protein modeling suggests that the effect of this mutation is a subtle one which affect the local polarity of the crystallin molecule surface, and may affect the manner of interaction between γD -crystallin protein and other proteins.更多还原