Cataracts are the leading cause of blindness in the world, and are formed upon aggregation of lens proteins into high molecular weight complexes, causing light scattering and lens opacity. Several studies implicate metals as a potential etiological agent for cataract, while copper and zinc concentrations in the cataractous lenses are increased significantly, as compared to normal lenses. The monomeric all β-sheet human γ-crystallins are among the most abundant crystallins in the lens and one of the most stable proteins in the human body, but its non-amyloid aggregation is associated with cataracts. In this presentation, the effect of metal ions in the aggregation of these proteins will be discussed. Specifically, Cu(II) and Zn(II) ions induce this aggregation, suggesting site-specific interactions with the γ-crystallins. The mechanism for metal-induced aggregation involves partial unfolding. Recent advances in understanding the nature of the metal-protein interactions associated to Cu- and Zn- induced aggregation of the γ-crystallins will be presented. Also, the effect of heavy metal ions on the aggregation of the γ-crystallins will be discussed. Metal-induced aggregation could be a physiologically relevant phenomenon; understanding its mechanism will help elucidate the role of metal ions in the aggregation of human crystallins and their potential involvement in the development of cataracts, providing important insights into the unexplored bioinorganic facet of this disease.

Metal-induced aggregation of human gamma-crystallins: Relevance to cataracts disease

254th National Meeting (2017)

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