人γD-晶状体蛋白及其五种突变型的分子特性比较  

Comparison on Molecular Characteristics of Human Gamma D-crystallin Protein and Its Five Mutations

作　　者：刘臻臻[1] 吴明星[1] 

机构地区：[1]中山大学中山眼科中心,中山大学眼科学国家重点实验室,广州510060

出　　处：《眼科学报》2007年第3期129-135,共7页Eye Science

基　　金：国家自然科学基金资助项目(No.30572003)

摘　　要：目的:运用生物信息学方法对人γD-晶状体蛋白(γD-crystallin,CRYGD)及其与遗传性白内障相关的五种突变型进行比较,通过对其编码蛋白的结构和功能的预测,探讨这些突变引起白内障的可能机制。方法:利用生物信息学相关网站中的蛋白质序列和结构信息以及各种分析软件,分析野生型CRYGD蛋白质及其五种突变型(R14C、P23T、R36S、R58H和W156X)的理化特性、翻译后的修饰、功能域、二级结构和三级结构等。结果:R14C、R36S、R58H和W156X等电点较野生型低;R14C较野生型多一暴露于分子表面的半胱氨酸残基;R14C、R36S、R58H突变局部电荷减少、疏水性增加;P23T局部柔性增加;R58H分子局部温度降低。结论:CRYGD突变表达的变异蛋白质可通过影响分子表面电荷、疏水性和空间结构导致蛋白沉积形成白内障。Objective ： To gain further information on the mechanisms underling the cataractogenesis by bioinformatics analysis on molecular characteristics of γ D-crystallin （CRYGD） protein and its five cataract-associated mutations. Methods： With the analyzing software in bioinformatics webs site, we analyzed the human wild-type CRYGD protein and the five reported mutations （R14C, P23T, R36S, R58H and W156X）, focusing on their physical-chemical characteristics, epitopes, post-translational modification sites, functional domains, secondary and tertiary structure. Result： R14C, R36S, R58H and W156X mutations resulted in a decrease in isoelectric point. R14C brought about a new cysteine residue exposed on the molecular surface. A decrease in local charge and a rise in local hydrophobicity was found in R14C, R36S and R58H. Local flexibility increased in P23T, while R58H caused a fall in local temperature. Conclusion： The mutations were shown to cause changes in protein surface polarity,hydrophobicity, and spatial structure, contributing to protein deposition and cataract formation.

关 键 词：γ D-晶状体蛋白 遗传性白内障 生物信息学 基因突变 

分 类 号：R776[医药卫生—眼科]