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The role of alpha-crystallin, a small heat-shock protein and chaperone, may explain how the lens stays transparent for so long. alpha-Crystallin prevents the aggregation of other lens crystallins and proteins that have become unfolded by 'trapping' the protein in a high-molecular-mass complex. However, during aging, the chaperone function of alpha-crystallin becomes compromised, allowing the formation of light-scattering aggregates that can proceed to form cataracts. Within the central part of the lens there is no turnover of damaged protein, and therefore post-translational modifications of alpha-crystallin accumulate that can reduce chaperone function; this is compounded in cataract lenses. Extensive in vitro glycation, carbamylation and oxidation all decrease chaperone ability. In the present study, we report the effect of the modifiers malondialdehyde, acetaldehyde and methylglyoxal, all of which are pertinent to cataract. Also modification by aspirin, which is known to delay cataract and other diseases, has been investigated. Recently, two point mutations of arginine residues were shown to cause congenital cataract. 1,2-Cyclohexanedione modifies arginine residues, and the extent of modification needed for a change in chaperone function was investigated. Only methylglyoxal and extensive modification by 1,2-cyclohexanedione caused a decrease in chaperone function. This highlights the robust nature of alpha-crystallin.

A major stress protein, α‐crystallin, functions as a chaperone. Site‐directed mutagenesis has been used to identify regions of the protein necessary for chaperone function. In this work we have taken some of the previously described mutants produced and assessed their chaperone function by both a traditional heat‐induced aggregation method at elevated temperature and using enzyme methods at 37 °C. In general the different assays gave parallel results indicating that the same property is being measured. Discrepancies were explicable by the heat lability of some mutants. Most mutants had full chaperone function showing the robust nature of α‐crystallin. A mutant corresponding to a minor component of rodent αA‐crystallin, αAins‐crystallin, had decreased chaperone function. Decreased chaperone function was also found for human Ser139→ Arg, Thr144→Arg, Ser59→Ala mutants of αB‐crystallin and double mutants Ser45→Ala/Ser59→Ala, Lys103→ Leu/His104→Ile, and Glu110→His/His111→Glu. A mutant Phe27→Arg that was the subject of previous controversy was shown to be fully active at physiological temperatures.