The lens proteins consist of about 95% crystallins (CRYs). The lens continues to grow throughout life, forming new fiber cells at the periphery of lens without ever replacing the older cells. As a consequence, the cells in the nucleus of the lens contain proteins that are as old as the animal itself.

To warrant transparency, the light-scattering orangelles, including the nuclei, are broken down in the later stages of differentiation. The transparency and high refractive index of the normal lens is achieved by a regular arrangement of the lens fiber cells during growth of the lenticular body and by the high concentration and the supramolecular organization of the lens-specific proteins, the crystallins, within each fiber cell.

In the mammalian lens, 3 major classes of crystallins are distinguished: alpha (CRYAs), beta (CRYBs), and gamma (CRYGs).

CRYAs

The largest, alpha-crystallin (CRYAs), is composed of 2 primary gene products--alpha-A (CRYAA) and alpha-B (CRYAA) (MIM.123590). Alpha-crystallin is composed of acidic and basic polypeptides designated alpha-A (CRYAA) and alpha-B (CRYAA), respectively. These show 57% amino acid homology.

Alpha-crystallin shows an intriguing relationship with the ubiquitous small heat-shock proteins (Wistow, 1985). The alpha-crystallins show homology with the small heat-shock proteins of Drosophila and soybean (Schoffl et al., 1984.) Heat-shock proteins (HSPs) form aggregates, as do alpha-crystallins, and are thought to protect cellular components under conditions of stress. Perhaps alpha-crystallin exerts a similar, as yet unknown stabilizing or protective effect in the lens fiber cells, which have to maintain a life-long resistance against deleterious influences.

CRYBs

At least 5 distinct polypeptides are involved in the oligomeric beta-crystallins (CRYBs) (MIM.123610).

CRYGs

The gamma-crystallins (CRYGs) (MIM.123660), which constitute about 40% of the total protein of the rodent lens, are monomeric; at least 5 closely related gamma crystallins have been identified in bovine and rat lens. In the rat, 2 distinct gamma-crystallin genes showed extensive sequence homology suggesting derivation from a common primordial gene (Moormann et al., 1982).

On the other hand, the superfamily of the beta- (CRYBs) and gamma-crystallins (CRYGs) shows structural similarities with a bacterial spore coat protein.

Members

Pathology (crystallinopathies)

 germline mutations in

• autosomal dominant desmin-related myopathy and lens opacities (MIM.608810)
• autosomal dominant posterior polar cataract (CPP2)
• autosomal dominant desmin-related myopathy

References

 Head MW, Goldman JE. Small heat shock proteins, the cytoskeleton, and inclusion body formation. Neuropathol Appl Neurobiol. 2000 Aug;26(4):304-12. PMID: #10931363#

 Clark JI, Muchowski PJ. Small heat-shock proteins and their potential role in human disease. Curr Opin Struct Biol. 2000 Feb;10(1):52-9. PMID: #10679464#

Members

 alpha-crystallins
 beta-crystallins