Accelerated oxidative aging in deamidated variants of the human eye lens protein γ(S)-crystallin

Abstract

Cataract disease causes clouding of the eye lens due to precipitation of lens proteins, known as crystallins. In aged and cataractous lenses, crystallins have been shown to accumulate post-translational modifications (PTMs), with deamidation and oxidation among the most commonly reported PTMs. Both deamidation and oxidation appear to promote crystallin aggregation; however, the relationship between these two modifications and their role in crystallin insolubility is not clear. We determined six novel crystal structures of a major human lens protein, γS-crystallin (γS): one of the wild-type in a monomeric state, and five of deamidated γS variants, ranging from three to nine deamidation sites, after varying degrees of sample aging.