FUNCTIONAL ELEMENTS IN ALPHA CRYSTALLIN CHAPERONE

描述：白内障是世界上致盲的主要原因。然而， 白内障形成的病因学知之甚少。最近才能 晶状体蛋白的主要成分a-晶状体蛋白抑制 其他蛋白质的聚集和沉淀(伴侣样活性) 已经被证明了。此外，还表明，α-晶状体蛋白 从高相对分子质量的晶状体和不溶于水的晶体中分离得到 组分具有较低的伴侣样活性。在此基础上 观察到，已经假设了星状细胞的类似伴侣的活动 A-晶状体蛋白对维持晶状体透明度至关重要， α-晶状体蛋白伴侣功能的失败导致非特异性 受损晶状体蛋白聚集与白内障的发生。为了更好地 了解α-晶体蛋白的伴侣样活性，PI建议 测定α-晶状体蛋白结合部位的氨基酸序列 使用模型蛋白质和新型交联剂的伴侣样功能。 本研究中使用的模式蛋白是酵母醇脱氢酶， Bb2-晶体蛋白和y2-晶体蛋白。此外，还将进行实验，以 确定在各种蛋白质中是否有共同的特征 在伴侣作用过程中与α-晶状体蛋白相互作用。的其他具体目标 这项建议包括a)确定委员会的数目和组成 A-晶体蛋白中的疏水位点已被牵连到 伴侣样活性和蛋白质聚集，b)研究是否 疏水中心也是a-晶体蛋白和c)中的伴侣中心。 α-晶状体蛋白的伴侣活性和疏水部位的研究 存在于晶状体中的水不溶部分。

DESCRIPTION: Cataract is a major cause of blindness in the world. Yet the etiology of cataract formation is poorly understood. Recently the ability of a-crystallin, the major component of lens proteins to suppress the aggregation and precipitation of other proteins (chaperone-like activity) has been demonstrated. furthermore, it has been shown that a-crystallin isolated from lens high molecular weight as well as from water-insoluble fraction has lower chaperone-like activity. On the basis of those observations it has been hypothesized that the chaperone-like activity of a-crystallin is crucial for the maintenance of lens transparency and that failure of a-crystallin chaperone-like function results in non-specific aggregation of damaged lens proteins and development of cataract. To better understand the chaperone-like activity of a-crystallin the PI proposes to determine the amino acid sequences in a-crystallin binding site during chaperone-like function using model proteins and novel crosslinking agents. The model proteins to be used in this study are yeast alcohol dehydrogenase, BB2-crystallin and y2-crystallin. Additionally experiments will be done to determine whether there are common features in various proteins that interact with a-crystallin during chaperone action. Other specific aims of this proposal include a) the determination of the number and make up of the hydrophobic sites in a-crystallin that have been implicated in chaperone-like activity and protein aggregation, b) investigation to see if the hydrophobic sites are also the chaperone sites in a-crystallin and c) studies on of chaperone-like activity and hydrophobic sites of a-crystallin present in lens water-insoluble fraction.