Structure and modifications of the junior chaperone alpha-crystallin. From lens transparency to molecular pathology

Eur J Biochem. 1994 Oct 1;225(1):1-19. doi: 10.1111/j.1432-1033.1994.00001.x.


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.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Cattle
  • Crystallins / biosynthesis
  • Crystallins / chemistry*
  • Crystallins / metabolism*
  • Heat-Shock Proteins / chemistry*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Lens, Crystalline / pathology
  • Lens, Crystalline / physiology*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Sequence Homology, Amino Acid
  • Vertebrates


  • Crystallins
  • Heat-Shock Proteins