The lens is formed from two protein superfamilies, the α- and βγ-crystallins. Representative three-dimensional structures show they both have a basic 2-β-sheet domain fold, with the βγ-domain being made from two intercalating Greek keys. X-ray structures of monomeric γ-crystallins and simple oligomeric β-crystallins show how multiple gene duplications can give rise to highly symmetrical assemblies based on paired domains. These protein folds have been engineered by directed mutagenesis to investigate the roles of the critical region in domain pairing and assembly. Inherited human cataracts have been described that are associated with representatives of each of the crystallin protein families. Mutations to certain β- and γ-crystallin genes cause expression of truncated polypeptides that would not be expected to fold properly; instead they would randomly aggregate causing light scattering. As crystallin proteins are not renewed, age-related cataract is a gradual accumulation of small changes to preexisting normal proteins. The precise sites of post-translational modifications are now being mapped to the various crystalline.
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