STRUCTURAL PERTURBATION OF ALPHA-CRYSTALLIN AND ITS CHAPERONE-LIKE ACTIVITY

alpha-Crystallin is a multimeric lenticular protein that has recently been shown to be expressed in several non-lenticular tissues as well. It is shown to prevent aggregation of non-native proteins as a molecul ar chaperone. By using a non-thermal aggregation model, we could show that this process is temperature-dependent. We investigated the chaper one-like activity of alpha-crystallin towards photo-induced aggregatio n of gamma-crystallin, aggregation of insulin and on the refolding ind uced aggregation of beta- and gamma-crystallins. We observed that alph a-crystallin could prevent photo-aggregation of gamma-crystallin and t his chaperone-like activity of alpha-crystallin is enhanced several fo ld at temperatures above 30 degrees C. This enhancement parallels the exposure of its hydrophobic surfaces as a function of temperature, pro bed using hydrophobic fluorescent probes such as pyrene and 8-anilinon aphthalene-1-sulfonate. We, therefore, concluded that alpha-crystallin prevents the aggregation of other proteins by providing appropriately placed hydrophobic surfaces; a structural transition above 30 degrees C involving enhanced or re-organized hydrophobic surfaces of alpha-cr ystallin is important for its chaperone-like activity. We also address ed the issue of conformational aspects of target proteins and found th at their aggregation prone molten globule states bind to alpha-crystal lin. We trace these developments and discuss some new lines that sugge st the role of tertiary structural aspects in the chaperone process. ( C) 1998 Elsevier Science B.V. All rights reserved.