FUNCTIONAL ELEMENTS IN ALPHA CRYSTALLIN CHAPERONE

ALPHA Crystallin Chaperone 中的功能元素

• 批准号: 6151082
• 负责人: KRISHNA K SHARMA
• 金额: $ 17.54万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6151082
• 关键词: alcohol dehydrogenase; chemical binding; crystallins; molecular chaperones; protein sequence; protein structure function

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.

描述：白内障是世界上导致失明的主要原因。 然而 白内障形成的病因尚不清楚。 最近的能力 a-晶状体蛋白，晶状体蛋白的主要成分，可抑制 其他蛋白质的聚集和沉淀（分子伴侣样活性） 已被证明。 此外，已经表明，a-晶状体蛋白 从高分子量镜片以及水不溶性物质中分离出来 部分具有较低的类伴侣活性。 在此基础上 观察结果推测，类似伴侣的活动 a-晶状体蛋白对于维持晶状体透明度至关重要， a-晶状体蛋白伴侣样功能的失败导致非特异性 受损晶状体蛋白的聚集和白内障的发生。 为了更好 了解 PI 建议的 a-晶状体蛋白的类似伴侣活性 确定a-晶状体蛋白结合位点的氨基酸序列 使用模型蛋白和新型交联剂实现类似伴侣的功能。 本研究中使用的模型蛋白是酵母乙醇脱氢酶， BB2-晶状体蛋白和y2-晶状体蛋白。 此外还将进行实验 确定各种蛋白质是否存在共同特征 在伴侣作用期间与α-晶状体蛋白相互作用。 其他具体目标 该提案包括 a) 确定 α-晶状体蛋白中的疏水位点与 分子伴侣样活性和蛋白质聚集，b) 调查是否 疏水位点也是 a-晶状体蛋白中的伴侣位点和 c) α-晶状体蛋白的分子伴侣活性和疏水位点的研究 存在于镜片的水不溶部分中。