Temperature-dependent chaperone activity and structural properties of human alpha A- and alpha B-crystallins

The chaperone activity and biophysical properties of recombinant human alph a A- and alpha B-crystallins were studied by light scattering and spectrosc opic methods. While the chaperone function of alpha A-crystallin markedly i mproves with an increase in temperature, the activity of alpha B homopolyme r appears to change very little upon heating. Compared with alpha B-crystal lin, the alpha A-homopolymer is markedly less active at low temperatures, b ut becomes a more active species at high temperatures. At physiologically r elevant temperatures, the alpha B homopolymer appears to be modestly (two t imes or less) more potent chaperone than alpha A homopolymer, In contrast t o very similar thermotropic changes in the secondary structure of both homo polymers, alpha A- and alpha B-crystallins markedly differ with respect to the temperature-dependent surface hydrophobicity profiles, Upon heating, al pha A-crystallin undergoes a conformational transition resulting in the exp osure of additional hydrophobic sites, whereas no such transition occurs fo r alpha B-crystallin, The correlation between temperature-dependent 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. Howeve r, the present data also show that the surface hydrophobicity is not the so le determinant of the chaperone function of alpha-crystallin.