Lens crystallins and oxidation:: the special case of γS

Among lens crystallins, gamma -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 gamma -crystallins. At pH 7.0, all the gamma -crystallins under study were checked to have the same structure in solution. Under gentle oxidation conditions at pH 8.0, human gammaS (h gammaS) and bovine gammaS (b gammaS) formed disulfide-linked dimers, whereas the other b gamma -crystallins did not. Cys20 was shown to be responsible for dimer formation since the C20S mutant only formed monomers. The h gammaS dimers were stable for weeks and did not form higher oligomers. In contrast, monomeric gammaS-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 gammaS-crystallins lack the temperature-induced opacification observed with the other gamma -crystallins and known as cold cataract. The oxidation-induced associative behaviour and cold cataract are therefore demonstrated to be uncoupled. (C) 2001 Elsevier Science B.V. All rights reserved.