| Abstrakt: |
Accessible sulfhydryls of cysteine residues are likely sites of reaction in long-lived proteins such as human lens crystallins. Disulfide bonding between cysteines is a major contributor to intermolecular cross-linking and aggregation of crystallins. A recently reported modification of γS-crystallins, S-methylation of cysteine residues, can prevent disulfide formation. The aim of this study was to determine whether cysteines in γC-, γD-, and γB-crystallins are also S-methylated. Our data show that all the γ-crystallins are S-methylated, but only at specific cysteines. In γD-crystallin, methylation is exclusively at Cys 110, whereas in γC- and γB-crystallins, the principal methylation site is Cys 22 with minor methylation at Cys 79. γD-crystallin is the most heavily methylated γ-crystallin. γD-Crystallins from adult lenses are 37%-70% methylated, whereas γC and γB are ∼12% methylated. The specificity of γ-crystallin methylation and its occurrence in young clear lenses supports the idea that inhibition of disulfide bonding by S-methylation may play a protective role against cataract. Another modification, not reported previously, is carbamylation of the N termini of γB-, γC-, γD-crystallins. N-terminal carbamylation is likely a developmentally related modification that does not negatively impact crystallin function. [ABSTRACT FROM AUTHOR] |
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