Deamidation in Human γS-Crystallin from Cataractous Lenses Is Influenced by Surface Exposure

• Published in: Biochemistry (Easton) Vol. 41; no. 27; pp. 8638 - 8648
• Main Authors: Lapko, Veniamin N, Purkiss, Andrew G, Smith, David L, Smith, Jean B
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09-07-2002
• Subjects: Amides - metabolism; Amino Acid Sequence; Cataract - metabolism; Chromatography, Ion Exchange; Crystallins - chemistry; Crystallins - isolation & purification; Crystallins - metabolism; Dithiothreitol - pharmacology; Humans; Lens, Crystalline - metabolism; Mass Spectrometry; Molecular Sequence Data; Oxidation-Reduction; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Trypsin
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi015924t

A major component of human nuclear cataracts is water-insoluble, high molecular weight protein. A significant component of this protein is disulfide bonded γS-crystallin that can be reduced to monomers by dithiothreitol. Analysis of this reduced γS-crystallin showed that deamidation of glutamine and asparagine residues is a principal modification. Deamidation is one of the modifications of lens crystallins associated with aging and cataractogenesis. One proposed hypothesis of cataractogenesis is that it develops in response to altered surface charges that cause conformational changes, which, in turn, permit formation of disulfide bonds and crystallin insolubility. This report, showing deamidation among the disulfide bonded γS-crystallins from cataractous lenses, supports this hypothesis.