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R. J. W. Truscott, P. Hains; Deamidation of Crystallins From Human Lenses. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2099.
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To characterise deamidation of crystallins in the human lens as a function of age.
Proteomic techniques were employed involving tryptic digestion, 2D chromatography and analysis of the digests using FT mass spectrometry. Older normal (age ~ 60 years) and age-matched nuclear cataract lenses were examined.
The sites of deamidation in all nine major human lens crystallins were mapped. Approximately equal numbers of glutamine and asparagine residues were found to be deamidated in older lenses, however the extent of deamidation of Asn was three times greater than that of Gln (Asn 22.6 +/- 3.6%; Gln 6.6 +/- 1.3%). Individual crystallins differed markedly in their extent of deamidation, and deamidated residues were typically localised within discrete regions of the polypeptides. Generally the sites of deamidation were similar in normal and cataract lenses with a suggestion of greater deamidation in cataract crystallins near terminal regions, which may reflect localised unfolding.
Deamidation is the most prevalent post-translational modification in proteins from older human lenses, and deamidation of susceptible asparagine and glutamine residues is likely to lead to unfolding of these proteins. Since the crystallins are present for our entire lives, deamidation is likely to be a key factor in age-related denaturation of such life-long proteins. Crystallin unfolding is implicated in ocular conditions such as presbyopia and age-related nuclear cataract.
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