Structure of the crystallins

The lens is formed from two protein superfamilies, the alpha- and beta gamm a-crystallins. Representative three-dimensional structures show they both h ave a basic 2-beta-sheet domain fold, with the py-domain being made from tw o intercalating Greek keys. X-ray structures of monomeric gamma-crystallins and simple oligomeric beta-crystallins show how multiple gene duplications can give rise to highly symmetrical assemblies based on paired domains. Th ese protein folds have been engineered by directed mutagenesis to investiga te the roles of the critical region in domain pairing and assembly. Inherit ed human cataracts have been described that are associated with representat ives of each of the crystallin protein families. Mutations to certain beta- and gamma-crystallin genes cause expression of truncated polypeptides that would not be expected to fold properly; instead they would randomly aggreg ate causing light scattering. As crystallin proteins are not renewed, age-r elated cataract is a gradual accumulation of small changes to preexisting n ormal proteins. The precise sites of post-translational modifications are n ow being mapped to the various crystallins.