title: Structure of the crystallins.
abstract: The lens is formed from two protein superfamilies, the alpha- and beta gamma-crystallins. Representative three-dimensional structures show they both have a basic 2-beta-sheet domain fold, with the beta gamma-domain being made from two 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. 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 beta- and gamma-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 pre-existing normal proteins. The precise sites of post-translational modifications are now being mapped to the various crystallins.
authors.affiliation: Birkbeck College, Department of Crystallography, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Slingsby
authors.forename: N J
authors.initials: NJ
authors.lastname: Clout
mesh_terms: D000595:Amino Acid Sequence; D002386:Cataract / Q000235:genetics / Q000378:metabolism*; D003459:Crystallins / Q000737:chemistry* / Q000235:genetics; D006360:Heat-Shock Proteins / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D003459:Crystallins; D006360:Heat-Shock Proteins