Eye lens αA- and αB-crystallin:: complex stability versus chaperone-like activity

The major lens protein alpha-crystallin is composed of two related types of subunits, alpha A- and alpha B-crystallin, of which the former is essentially lens-restricted, while the latter also occurs in various other tissues. With regard to their respective chaperone capacities, it has been reported that homomultimeric alpha A-crystallin complexes perform better in preventing thermal aggregation of proteins, while alpha B-crystallin complexes protect more efficiently against reduction-induced aggregation of proteins. Here, we demonstrate that this seeming discrepancy is solved when the reduction assay is performed at increasing temperatures: above 50 degrees C alpha A- performs better than alpha B-crystallin also in this assay. This inversion in protective capacity might relate to the greater resistance of aa-crystallin to heat denaturation. Infrared spectroscopy, however, revealed that this is not due to a higher thermostability of alpha A-crystallin's secondary structure. also the accessible hydrophobic surfaces do not account for the chaperoning differences of alpha A- and alpha B-crystallin, since regardless of the experimental temperature alpha B-crystallin displays a higher hydrophobicity. It is argued that the greater complex stability of alpha A-crystallin, as evident upon urea denaturation, and the higher chaperone capacity of alpha B-crystallin at physiological temperatures reflect the evolutionary compromise to obtain an optimal functioning of heteromeric alpha-crystallin as a lens protein. (C) 1999 Elsevier Science B.V. All rights reserved.