Temperature-dependent Chaperone Activity and Structural Properties of Human aA- and aB-crystallins*

The chaperone activity and biophysical properties of recombinant human aAand aB-crystallins were studied by light scattering and spectroscopic methods. While the chaperone function of aA-crystallin markedly improves with an increase in temperature, the activity of aB homopolymer appears to change very little upon heating. Compared with aB-crystallin, the aA-homopolymer is markedly less active at low temperatures, but becomes a more active species at high temperatures. At physiologically relevant temperatures, the aB homopolymer appears to be modestly (two times or less) more potent chaperone than aA homopolymer. In contrast to very similar thermotropic changes in the secondary structure of both homopolymers, aAand aBcrystallins markedly differ with respect to the temperature-dependent surface hydrophobicity profiles. Upon heating, aA-crystallin undergoes a conformational transition resulting in the exposure of additional hydrophobic sites, whereas no such transition occurs for aB-crystallin. The correlation between temperaturedependent changes in the chaperone activity and hydrophobicity properties of the individual homopolymers supports the view that the chaperone activity of a-crystallin is dependent on the presence of surface-exposed hydrophobic patches. However, the present data also show that the surface hydrophobicity is not the sole determinant of the chaperone function of a-crystallin.