The human lens has a protein concentration of 33% of its wet weight, which is at least twice the concentration found in most tissues. Lens proteins are commonly divided into 2 groups, based on water solubility (Fig 3-1); the ratio of these 2 groups changes with increasing age. Water-soluble proteins account for approximately 80% of lens proteins in a young lens; with increasing age, the percentage of water-insoluble proteins increases. The water-soluble group consists mainly of a group of proteins called crystallins. The crystallins can be divided into 2 major groups, α-crystallins and β,γ-crystallins.
α-Crystallins are the largest of the crystallins. In their native state, their molecular mass ranges between 600 and 800 kilodaltons (kDa); they represent about one-third of the lens proteins by mass. They may also combine with other crystallins, yielding complexes greater than 2 × 106. There are 2 α-crystallin subunits, αA and αB, each with a molecular mass of approximately 20 kDa, which form heteromeric complexes containing about 30 subunits. The α-crystallins are members of the family of small heat-shock proteins; their complexes bind to partially denatured proteins and prevent them from aggregating. Their primary function in lens fiber cells appears to be to inhibit the complete denaturation and insolubilization of the other crystallins.
Figure 3-1 Overview of lens proteins.
The basic structure of the β-crystallins and γ-crystallins has been maintained through hundreds of millions of years of vertebrate evolution. X-ray studies have demonstrated fourfold repetition of a core 3-dimentional structural motif, suggesting that the β,γ-crystallins might have arisen from double duplication and fusion of a gene for a 40-residue polypeptide. β,γ-Crystallins are subdivided into 2 groups, based on molecular mass and isoelectric points.
The β-crystallins, a complex group of oligomers composed of polypeptides, are encoded by 7 genes. Their molecular masses range from 23 to 32 kDa. The individual polypeptides associate with each other, forming dimers and higher-order complexes in their native state. By gel chromatography, the β-crystallins can be separated into βH (β high-molecular-mass) and βL (β low-molecular-mass) fractions.
The γ-crystallins are the smallest of the crystallins, with a molecular mass in the range of 20 kDa or less. In humans, the gamma family is encoded by 4 genes. Because the native γ-crystallins do not associate with each other or with other proteins, they have the lowest molecular mass of the crystallin fractions.
Excerpted from BCSC 2020-2021 series: Section 11 - Lens and Cataract. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.