Lens crystallins and oxidation: the special case of γS

Abstract

Among lens crystallins, γ-crystallins are particularly sensitive to oxidation, because of their high amount of Cys and Met residues. They have the reputation to induce, upon ageing, lens structural modifications leading to opacities. A combination of small angle X-ray scattering and chromatography was used to study the oxidation of γ-crystallins. At pH 7.0, all the γ-crystallins under study were checked to have the same structure in solution. Under gentle oxidation conditions at pH 8.0, human γS (hγS) and bovine γS (bγS) formed disulfide-linked dimers, whereas the other bγ-crystallins did not. Cys20 was shown to be responsible for dimer formation since the C20S mutant only formed monomers. The hγS dimers were stable for weeks and did not form higher oligomers. In contrast, monomeric γS-crystallins freshly prepared at pH 8.0, and submitted to more drastic oxidation by X-ray induced free radicals, were rapidly transformed into higher oligomers. So, only extensive oxidation causing partial unfolding could be detrimental to the lens and linked to cataract formation. The γS-crystallins lack the temperature-induced opacification observed with the other γ-crystallins and known as cold cataract. The oxidation-induced associative behaviour and cold cataract are therefore demonstrated to be uncoupled.