title: Modifications of human betaA1/betaA3-crystallins include S-methylation, glutathiolation, and truncation.
abstract: Disulfide bonding of lens crystallins contributes to the aggregation and insolubilization of these proteins that leads to cataract. A high concentration of reduced glutathione is believed to be key in preventing oxidation of crystallin sulfhydryls to form disulfide bonds. This protective role is decreased in aged lenses because of lower glutathione levels, especially in the nucleus. We recently found that human gamma-crystallins undergo S-methylation at exposed cysteine residues, a reaction that may prevent disulfide bonding. We report here that betaA1/A3-crystallins are also methylated at specific cysteine residues and are the most heavily methylated of the human lens crystallins. Among the methylated sites, Cys 64, Cys 99, and Cys 167 of betaA1-crystallin, methylation at Cys 99 is highest. Cys 64 and Cys 99 are also glutathiolated, even in a newborn lens. These post-translational modifications of the exposed cysteines may be important for maintaining the crystallin structure required for lens transparency. Previously unreported N-terminal truncations were also found.
authors.affiliation: Department of Chemistry, Hamilton Hall, University of Nebraska-Lincoln, Lincoln, NE 68588-0304, USA.
authors.forename: Veniamin N
authors.initials: VN
authors.lastname: Lapko
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Cerny
authors.forename: David L
authors.initials: DL
authors.lastname: Smith
authors.forename: Jean B
authors.initials: JB
authors.lastname: Smith
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn; D008745:Methylation; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D038204:beta-Crystallins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*
chemical_list: D038204:beta-Crystallins; D005978:Glutathione