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.
Showing the most recent 10 out of 32 publications
