抄録
A cataract is a clouding of the lens in the eye that affects vision. The one of the cause of the cataracts may be due to the abnormal aggregation of protein in lens. We found that two specific aspartyl (Asp) residues in αA- and αB-crystallins, respectively and one specific Asp in βB2-crystallin, from human eye lenses invert to the D-β-isomers to high degree during aging. The appearance of D-β-Asp isomers in proteins can cause major changes in the corresponding 3-D structure. Therefore, the presence of these isomers may be one of the triggers for abnormal aggregation, leading to cataracts. In fact, αA-crystallin containing large amounts of D-β-Asp obtained from cataractous patients of ～ 80 years of age has been shown to undergo increased aggregation to form massive and heterogeneous aggregates. Moreover, its chaperon activity, which prevents aggregation and insolubilization of other lenticular proteins, is reduced by 40%. Here we describe three important aspects of our research: (i) a method for detecting D-β-Asp at specific sites in particular proteins, (ii) a likely spontaneous mechanism by which Asp residues in proteins invert and isomerize to the D-β-form, (iii) a discussion of factors that favor such a reaction.
