title: Structure and modifications of the junior chaperone alpha-crystallin. From lens transparency to molecular pathology.
abstract: alpha-Crystallin is a high-molecular-mass protein that for many decades was thought to be one of the rare real organ-specific proteins. This protein exists as an aggregate of about 800 kDa, but its composition is simple. Only two closely related subunits termed alpha A- and alpha B-crystallin, with molecular masses of approximately 20 kDa, form the building blocks of the aggregate. The idea of organ-specificity had to be abandoned when it was discovered that alpha-crystallin occurs in a great variety of nonlenticular tissues, notably heart, kidney, striated muscle and several tumors. Moreover alpha B-crystallin is a major component of ubiquinated inclusion bodies in human degenerative diseases. An earlier excitement arose when it was found that alpha B-crystallin, due to its very similar structural and functional properties, belongs to the heat-shock protein family. Eventually the chaperone nature of alpha-crystallin could be demonstrated unequivocally. All these unexpected findings make alpha-crystallin a subject of great interest far beyond the lens research field. A survey of structural data about alpha-crystallin is presented here. Since alpha-crystallin has resisted crystallization, only theoretical models of its three-dimensional structure are available. Due to its long life in the eye lens, alpha-crystallin is one of the best studied proteins with respect to post-translational modifications, including age-induced alterations. Because of its similarities with the small heat-shock proteins, the findings about alpha-crystallin are illuminative for the latter proteins as well. This review deals with: structural aspects, post-translational modifications (including deamidation, racemization, phosphorylation, acetylation, glycation, age-dependent truncation), the occurrence outside of the eye lens, the heat-shock relation and the chaperone activity of alpha-crystallin.
authors.affiliation: Department of Biochemistry, University of Nijmegen, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Groenen
authors.forename: K B
authors.initials: KB
authors.lastname: Merck
authors.forename: W W
authors.initials: WW
authors.lastname: de Jong
authors.forename: H
authors.initials: H
authors.lastname: Bloemendal
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003459:Crystallins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000473:pathology / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid; D014714:Vertebrates
chemical_list: D003459:Crystallins; D006360:Heat-Shock Proteins