alpha-crystallin as a molecular chaperone

The role of alpha-crystallin as a molecular chaperone may explain how the l ens stays transparent for so long. alpha-Crystallin prevents the aggregatio n of other lens crystallins and proteins that have become unfolded by "trap ping" the protein in a high molecular weight complex. It also protects enzy me activities. The substrate protein may interact while in a molten globule state. alpha-Crystallin predominantly binds to proteins very early in the denaturation pathways. The amphiphilic nature of alpha-crystallin, a polar C-terminal-region and a hydrophobic N-terminal-region are all essential for chaperone function. The flexible C-terminal extension maintains solubility and can bind to opposing charged residues of unfolding proteins. Hydrophob ic regions in the :V-terminal region then hold the unfolded protein. Specif ic areas important for chaperone binding and function have been identified throughout the N-terminal-region, connecting peptide and C-terminal extensi on. After a substantial amount of chemical data and models, cryo-EM images of alpha-crystallin have confirmed a variable 3D surface with a hollow inte rior, alpha-Crystallin taken from the lens nucleus shows an age-dependent d ecrease in chaperone function. High molecular weight aggregates and alpha-c rystallin Found within the nucleus from clear and cataract lenses have redu ced chaperone function. Post-translational modifications, known to occur du ring ageing, such as glycation, carbamylation, oxidation, phosphorylation a nd truncation cause a decrease in chaperone function. alpha-Crystallin is e xpressed outside the lens. alpha B-Crystallin can be induced by heat shock in many tissues where it is translocated from cytoplasm to nucleus. Increas ed expression of alpha B-crystallin has been seen in many pathological stat es. Conformational disorders, including cataract may have a common aetiolog y and potentially a common therapy. (C) 1999 Elsevier Science Ltd. All righ ts reserved.