Protein Cleavage Sites In Experimental Cataractous Lens

Oregon Health And Science University, Portland OR

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Abstract

DESCRIPTION (provided by applicant): Post-translational modifications of crystallins, the major structural proteins of the lens, may be a major cause of opacification in cataract. This project will utilize tools developed in the emerging field of proteomics to detect and quantify crystallin modifications that include deamidation, oxidation, and proteolytic cleavage. This information will then be used to study how modification in crystallins alters the association properties of the proteins in vivo. The specific aims are to: 1. measure and quantify post-translational modifications in cystallins from normal lenses of increasing age using two-dimensional electrophoresis and mass spectrometry; 2. detect crystallin modifications unique to cataractous human lenses; 3. determine the functional significance of N-terminal extension loss in beta-crystallins by expressing both normal and N-terminally truncated forms of the human proteins. These studies are clinically relevant because characterization of post-translational modifications and their effect on crystallin behavior will play a key role in the future development of agents to slow the rate of cataract formation.