FUNCTIONAL ELEMENTS IN ALPHA CRYSTALLIN CHAPERONE

ALPHA Crystallin Chaperone 中的功能元素

• 批准号: 2872380
• 负责人: KRISHNA K SHARMA
• 金额: $ 17.03万
• 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 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2872380
• 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.

白内障是世界上致盲的主要原因之一。然而,