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Methylation and carbamylation of human γ‐crystallins
Author(s) -
Lapko Veniamin N.,
Smith David L.,
Smith Jean B.
Publication year - 2003
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0305403
Subject(s) - methylation , crystallin , chemistry , dna methylation , computational biology , biochemistry , biophysics , biology , dna , gene , gene expression
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.