Structure and Modifications of the Junior Chaperone α‐Crystallin: From Lens Transparency to Molecular Pathology

Abstract

α‐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 αA‐ and αB‐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 α‐crystallin occurs in a great variety of nonlenticular tissues, notably heart, kidney, striated muscle and several tumors. Moreover αB‐crystallin is a major component of ubiquinated inclusion bodies in human degenerative diseases. An earlier excitement arose when it was found that αB‐crystallin, due to its very similar structural and functional properties, belongs to the heat‐shock protein family. Eventually the chaperone nature of α‐crystallin could be demonstrated unequivocally. All these unexpected findings make α‐crystallin a subject of great interest far beyond the lens research field. A survey of structural data about α‐crystallin is presented here. Since α‐crystallin has resisted crystallization, only theoretical models of its three‐dimensional structure are available. Due to its long life in the eye lens, α‐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 α‐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 α‐crystallin.